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Section 2 - The Biology of Male Reproduction and Infertility

Published online by Cambridge University Press:  06 December 2023

Douglas T. Carrell
Affiliation:
Utah Center for Reproductive Medicine
Alexander W. Pastuszak
Affiliation:
University of Utah
James M. Hotaling
Affiliation:
Utah Center for Reproductive Medicine
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Men's Reproductive and Sexual Health Throughout the Lifespan
An Integrated Approach to Fertility, Sexual Function, and Vitality
, pp. 23 - 96
Publisher: Cambridge University Press
Print publication year: 2023

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References

Soumillon, M, Necsulea, A, Weier, M, et al. Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Rep. 2013;3(6):21792190.Google Scholar
Uhlen, M, Fagerberg, L, Hallstrom, BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.CrossRefGoogle ScholarPubMed
Pineau, C, Hikmet, F, Zhang, C, et al. Cell type-specific expression of testis elevated genes based on transcriptomics and antibody-based proteomics. J Proteome Res. 2019;18(12):42154230.CrossRefGoogle ScholarPubMed
Weinbauer, G, Luetjens, C, Simoni, M, Nieschlag, E. Physiology of testicular fuction. In: Nieschlag, E., Behre, HM, Nieschlag, S, eds. Andrology Male Reproductive Health and Dysfunction. 3rd ed. Springer-Verlag; 2010:1159.Google Scholar
Petersen, PM, Seieroe, K, Pakkenberg, B. The total number of Leydig and Sertoli cells in the testes of men across various age groups: a stereological study. J Anat. 2015;226(2):175179.Google Scholar
Ivell, R, Agoulnik, AI, Anand-Ivell, R. Relaxin-like peptides in male reproduction – a human perspective. Br J Pharmacol. 2017;174(10):9901001.Google Scholar
Prince, FP. The human Leydig cell. In: Payne, AH, Hardy, MP, eds. The Leydig Cell in Health and Disease. Humana Press; 2007:7189.CrossRefGoogle Scholar
Chen, P, Zirkin, BR, Chen, H. Stem Leydig cells in the adult testis: characterization, regulation and potential applications. Endocrine Reviews. 41(1):2232.CrossRefGoogle Scholar
Head, JR, Neaves, WB, Billingham, RE. Immune privilege in the testis. I. Basic parameters of allograft survival. Transplantation. 1983;36(4):423431.Google Scholar
Fijak, M, Pilatz, A, Hedger, MP, et al. Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice? Hum Reprod Update. 2018;24(4):416441.Google Scholar
Maekawa, M, Kamimura, K, Nagano, T. Peritubular myoid cells in the testis: their structure and function. Arch Histol Cytol. 1996;59(1):113.CrossRefGoogle ScholarPubMed
Arenas, MI, Bethencourt, FR, Fraile, B, Paniagua, R. Immunocytochemical and quantitative study of the tunica albuginea testis in young and ageing men. Histochem Cell Biol. 1997;107(6):469477.Google Scholar
Davidoff, MS, Breucker, H, Holstein, AF, Seidl, K. Cellular architecture of the lamina propria of human seminiferous tubules. Cell Tissue Res. 1990;262(2):253261.Google Scholar
Hargrove, JL, MacIndoe, JH, Ellis, LC. Testicular contractile cells and sperm transport. Fertil Steril. 1977;28(11):11461157.Google Scholar
Mayerhofer, A. Human testicular peritubular cells: more than meets the eye. Reproduction. 2013;145(5):R107R116.CrossRefGoogle ScholarPubMed
Volkmann, J, Muller, D, Feuerstacke, C, et al. Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts. Hum Reprod. 2011;26(6):14501461.Google Scholar
Sato, Y, Nozawa, S, Iwamoto, T. Study of spermatogenesis and thickening of lamina propria in the human seminiferous tubules. Fertil Steril. 2008;90(4):13101312.CrossRefGoogle ScholarPubMed
Johnson, L, Zane, RS, Petty, CS, Neaves, WB. Quantification of the human Sertoli cell population: its distribution, relation to germ cell numbers, and age-related decline. Biol Reprod. 1984;31(4):785795.CrossRefGoogle ScholarPubMed
Franca, LR, Hess, RA, Dufour, JM, Hofmann, MC, Griswold, MD. The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology. 2016;4(2):189212.Google Scholar
Setchell, BP. The secretion of fluid by the testes of rats, rams and goats with some observations on the effect of age, cryptorchidism and hypophysectomy. J Reprod Fertil. 1970;23(1):7985.Google Scholar
Stanton, PG. Regulation of the blood-testis barrier. Semin Cell Dev Biol. 2016;59:166173.Google Scholar
Mruk, DD, Cheng, CY. The mammalian blood-testis barrier: its biology and regulation. Endocr Rev. 2015;36(5):564591.Google Scholar
Makela, JA, Hobbs, RM. Molecular regulation of spermatogonial stem cell renewal and differentiation. Reproduction. 2019;158(5):R169R187.CrossRefGoogle ScholarPubMed
Santi, D, Crepieux, P, Reiter, E, et al. Follicle-stimulating hormone (FSH) action on spermatogenesis: a focus on physiological and therapeutic roles. J Clin Med. 2020;9(4):1014.Google Scholar
de Rooij, DG, Russell, LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl. 2000;21(6):776798.Google Scholar
Boitani, C, Di, PS, Esposito, V, Vicini, E. Spermatogonial cells: mouse, monkey and man comparison. Semin Cell Dev Biol. 2016;59:7988.Google Scholar
Clermont, Y. The cycle of the seminiferous epithelium in man. Am J Anat. 1963;112:3551.CrossRefGoogle ScholarPubMed
Rowley, MJ, Heller, CG. Quantitation of the cells of the seminiferous epithelium of the human testis employing the sertoli cell as a constant. Z Zellforsch Mikrosk Anat. 1971;115(4):461472.CrossRefGoogle ScholarPubMed
Clermont, Y. Renewal of spermatogonia in man. Am J Anat. 1966;118(2):509524.Google Scholar
Hermann, BP, Sukhwani, M, Hansel, MC, Orwig, KE. Spermatogonial stem cells in higher primates: are there differences from those in rodents? Reproduction. 2010;139(3):479493.Google Scholar
Clermont, Y. Two classes of spermatogonial stem cells in the monkey (Cercopithecus aethiops). Am J Anat. 1969;126(1):5771.CrossRefGoogle ScholarPubMed
van Alphen, MM, de Rooij, DG. Depletion of the seminiferous epithelium of the rhesus monkey, Macaca mulatta, after X-irradiation. Br J Cancer Suppl. 1986;7:102104.Google Scholar
Di Persio, S, Saracino, R, Fera, S, et al. Spermatogonial kinetics in humans. Development. 2017;144(19):34303439.Google Scholar
Sohni, A, Tan, K, Song, HW, et al. The neonatal and adult human testis defined at the single-cell level. Cell Rep. 2019;26(6):15011517.CrossRefGoogle ScholarPubMed
Muciaccia, B, Boitani, C, Berloco, BP, et al. Novel stage classification of human spermatogenesis based on acrosome development. Biol Reprod. 2013;89(3):60.Google Scholar
Nihi, F, Gomes, MLM, Carvalho, FAR, et al. Revisiting the human seminiferous epithelium cycle. Hum Reprod. 2017;32(6):11701182.Google Scholar
Clermont, Y, Bustos-Obregon, E. Re-examination of spermatogonial renewal in the rat by means of seminiferous tubules mounted “in toto.” Am J Anat. 1968;122(2):237247.CrossRefGoogle ScholarPubMed
Bolcun-Filas, E, Handel, MA. Meiosis: the chromosomal foundation of reproduction. Biol Reprod. 2018;99(1):112126.Google Scholar
Barchi, M, Mahadevaiah, S, Di, GM, et al. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol. 2005;25(16):72037215.Google Scholar
Tsai, MC, Cheng, YS, Lin, TY, Yang, WH, Lin, YM. Clinical characteristics and reproductive outcomes in infertile men with testicular early and late maturation arrest. Urology. 2012;80(4):826832.Google Scholar
Gershoni, M, Hauser, R, Barda, S, et al. A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest. Hum Reprod. 2019;34(4):666671.Google Scholar
Wyrwoll, MJ, Temel, SG, Nagirnaja, L, et al. Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility. Am J Hum Genet. 2020;107(2):342351.Google Scholar
Riera-Escamilla, A, Enguita-Marruedo, A, Moreno-Mendoza, D, et al. Sequencing of a ‘mouse azoospermia’ gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest. Hum Reprod. 2019;34(6):978988.Google Scholar
Jan, SZ, Jongejan, A, Korver, CM, et al. Distinct prophase arrest mechanisms in human male meiosis. Development. 2018;145(16).Google Scholar
Sarrate, Z, Sole, M, Vidal, F, Anton, E, Blanco, J. Chromosome positioning and male infertility: it comes with the territory. J Assist Reprod Genet. 2018;35(11):19291938.Google Scholar
Wang, Y, Wang, H, Zhang, Y, et al. Reprogramming of meiotic chromatin architecture during spermatogenesis. Mol Cell. 2019;73(3):547561.Google Scholar
Vara, C, Paytuvi-Gallart, A, Cuartero, Y, et al. Three-dimensional genomic structure and cohesin occupancy correlate with transcriptional activity during spermatogenesis. Cell Rep. 2019;28(2):352367.Google Scholar
Clermont, Y, Leblond, CP. Spermiogenesis of man, monkey, ram and other mammals as shown by the periodic acid-Schiff technique. Am J Anat. 1955;96(2):229253.Google Scholar
Lehti, MS, Sironen, A. Formation and function of the manchette and flagellum during spermatogenesis. Reproduction. 2016;151(4):R43R54.Google Scholar
Pleuger, C, Lehti, MS, Dunleavy, JE, Fietz, D, O’Bryan, MK. Haploid male germ cells-the Grand Central Station of protein transport. Hum Reprod Update. 2020;26(4):474500.CrossRefGoogle ScholarPubMed
Bao, J, Bedford, MT. Epigenetic regulation of the histone-to-protamine transition during spermiogenesis. Reproduction. 2016;151(5):R55R70.Google Scholar
Monesi, V. Ribonucleic acid synthesis during mitosis and meiosis in the mouse testis. J Cell Biol. 1964;22:521532.Google Scholar
Oliva, R. Protamines and male infertility. Hum Reprod Update. 2006;12(4):417435.Google Scholar
Carrell, DT, Emery, BR, Hammoud, S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update. 2007;13(3):313327.Google Scholar
Heller, CG, Clermont, Y. Spermatogenesis in man: an estimate of its duration. Science. 1963;140(3563):184186.Google Scholar
Russell, LD, Ettlin, RA, Hikim, APS, Clegg, ED. Histological and histopathological evaluation of the testis. J Androl. 1993;17(6):615627.Google Scholar
Heller, CH, Clermont, Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res. 1964;20:545575.Google Scholar
Suzuki, S, Diaz, VD, Hermann, BP. What has single-cell RNA-seq taught us about mammalian spermatogenesis? Biol Reprod. 2019;101(3):617634.CrossRefGoogle ScholarPubMed
Jan, SZ, Vormer, TL, Jongejan, A, et al. Unraveling transcriptome dynamics in human spermatogenesis. Development. 2017;144(20):36593673.Google Scholar
Shami, AN, Zheng, X, Munyoki, SK, et al. Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis. Dev Cell. 2020;54(4):529547.Google Scholar
Amann, RP. The cycle of the seminiferous epithelium in humans: a need to revisit? J Androl. 2008;29(5):469487.Google Scholar
Guo, J, Grow, EJ, Mlcochova, H, et al. The adult human testis transcriptional cell atlas. Cell Res. 2018;28(12):11411157.Google Scholar
Hermann, BP, Cheng, K, Singh, A, et al. The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids. Cell Rep. 2018;25(6):16501667.Google Scholar
Goldmann, JM, Veltman, JA, Gilissen, C. De novo mutations reflect development and aging of the human germline. Trends Genet. 2019;35(11):828839.CrossRefGoogle ScholarPubMed
Xia, B, Yan, Y, Baron, M, et al. Widespread transcriptional scanning in the testis modulates gene evolution rates. Cell. 2020;180(2):248262.Google Scholar
Svejstrup, JQ. Mechanisms of transcription-coupled DNA repair. Nat Rev Mol Cell Biol. 2002;3(1):2129.Google Scholar
Gille, AS, Lapoujade, C, Wolf, JP, Fouchet, P, Barraud-Lange, V. Contribution of single-cell transcriptomics to the characterization of human spermatogonial stem cells: toward an application in male fertility regenerative medicine? Int J Mol Sci. 2019;20(22):5773.Google Scholar
Soraggi, S, Riera, M, Rajpert-De, ME, Schierup, MH, Almstrup, K. Evaluating genetic causes of azoospermia: what can we learn from a complex cellular structure and single-cell transcriptomics of the human testis? Hum Genet. 2021;140(1):183201.Google Scholar

References

Fink, G. 60 years of neuroendocrinology: memoir: Harris’ neuroendocrine revolution: of portal vessels and self-priming. J Endocrinol. 2015;226:T13T24.Google Scholar
Schally, AV, Arimura, A, Kastin, AJ, et al. Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science. 1971;173:10361038.CrossRefGoogle ScholarPubMed
Plant, TM. 60 years of neuroendocrinology: the hypothalamo-pituitary-gonadal axis. J Endocrinol. 2015;226:T41T54.Google Scholar
Schally, AV. Use of GnRH in preference to LH-RH terminology in scientific papers. Hum Reprod. 2000;15:20592061.Google Scholar
Millar, RP. GnRHs and GnRH receptors. Anim Reprod Sci. 2005;88:528.Google Scholar
Okubo, K, Nagahama, Y. Structural and functional evolution of gonadotropin-releasing hormone in vertebrates. Acta Physiol (Oxf). 2008;193:315.Google Scholar
Kaprara, A, Huhtaniemi, IT. The hypothalamus-pituitary-gonad axis: tales of mice and men. Metabolism. 2018;86:317.Google Scholar
White, RB, Eisen, JA, Kasten, TL, Fernald, RD. Second form of gonadotropin-releasing hormone in humans. Proc Natl Acad Sci USA. 1998;95:305309.CrossRefGoogle ScholarPubMed
Densmore, VS, Urbanski, HF. Relative effect of gonadotropin releasing hormone (GnRH)-I and GnRH-II on gonadotropin release. J Clin Endocrinol Metab. 2003;88:21262134.Google Scholar
Lee, VH, Lee, LT, Chow, BK. Gonadotropin-releasing hormone: regulation of the GnRH gene. FEBS J. 2008;275:54585478.Google Scholar
Weinbauer, GF, Luetjens, CM, Simoni, M, Nieschlag, E. Physiology of testicular function. In: Nieschlag, E, Behre, HM, Nieschlag, S, eds. Andrology: Male Reproductive Health and Disfunction. 3rd ed. Springer-Verlag; 2010:1159.Google Scholar
Herbison, AE. Physiology of the adult gonadotropin-releasing hormone neuronal network. In: Plant, TM, Zeleznik, AJ, eds. Knobil and Neill’s Physiology of Reproduction. 5th ed. Elsevier Inc.; 2015:399467.Google Scholar
Clifton, DKS. Neuroendocrinology of reproduction. In: Strauss, JF, Barberi, RL, eds. Yen & Jaffe’s Reproductive Endocrinology. Elsevier; 2009: Ch. 1.Google Scholar
Schwanzel-Fukuda, M, Pfaff, DW. Origin of luteinizing hormone-releasing hormone neurons. Nature. 1989;338:161164.Google Scholar
Wierman, ME, Kiseljak-Vassiliades, K, Tobet, S. Gonadotropin-releasing hormone (GnRH) neuron migration: initiation, maintenance and cessation as critical steps to ensure normal reproductive function. Front Neuroendocrinol. 2011;32:4352.Google Scholar
Maeda, K, Ohkura, S, Uenoyama, Y, et al. Neurobiological mechanisms underlying GnRH pulse generation by the hypothalamus. Brain Res. 2010;1364:103115.Google Scholar
Moenter, SM, DeFazio, AR, Pitts, GR, Nunemaker, CS. Mechanisms underlying episodic gonadotropin-releasing hormone secretion. Front Neuroendocrinol. 2003;24:7993.Google Scholar
Carmel, PW, Araki, S, Ferin, M. Pituitary stalk portal blood collection in rhesus monkeys: evidence for pulsatile release of gonadotropin-releasing hormone (GnRH). Endocrinology. 1976;99:243248.Google Scholar
Antunes, JL, Carmel, PW, Housepian, EM, Ferin, M. Luteinizing hormone-releasing hormone in human pituitary blood. J Neurosurg. 1978;49:382386.CrossRefGoogle ScholarPubMed
Belchetz, PE, Plant, TM, Nakai, Y, Keogh, EJ, Knobil, E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science. 1978;202:631633.Google Scholar
Blumenfeld, Z. Investigational and experimental GnRH analogs and associated neurotransmitters. Expert Opin Investig Drugs. 2017;26:661667.Google Scholar
Moenter, SM, DeFazio, AR, Pitts, GR, Nunemaker, CS. Mechanisms underlying episodic gonadotropin-releasing hormone secretion. Front Neuroendocrinol. 2003;24:7993.Google Scholar
Martinez de la Escalera, G, Choi, AL, Weiner, RI. Generation and synchronization of gonadotropin-releasing hormone (GnRH) pulses: intrinsic properties of the GT1–1 GnRH neuronal cell line. Proc Natl Acad Sci USA. 1992;89:18521855.Google Scholar
Wilson, RC, Kesner, JS, Kaufman, JM, Uemura, T, Akema, T, Knobil, E. Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey. Neuroendocrinology. 1984;39:256260.Google Scholar
Ezzat, A, Pereira, A, Clarke, IJ. Kisspeptin is a component of the pulse generator for GnRH secretion in female sheep but not the pulse generator. Endocrinology. 2015;156:18281837.Google Scholar
Waldhauser, F, Weissenbacher, G, Frisch, H, Pollak, A. Pulsatile secretion of gonadotropins in early infancy. Eur J Pediatr. 1981;137:7174.CrossRefGoogle ScholarPubMed
Conte, FA, Grumbach, MM, Kaplan, SL, Reiter, EO. Correlation of luteinizing hormone-releasing factor-induced luteinizing hormone and follicle-stimulating hormone release from infancy to 19 years with the changing pattern of gonadotropin secretion in agonadal patients: relation to the restraint of puberty. J Clin Endocrinol Metab. 1980;50:163168.Google Scholar
Pohl, CR, deRidder, CM, Plant, TM. Gonadal and nongonadal mechanisms contribute to the prepubertal hiatus in gonadotropin secretion in the female rhesus monkey (Macaca mulatta). J Clin Endocrinol Metab. 1995;80:20942101.Google Scholar
Boyar, R, Finkelstein, J, Roffwarg, H, Kapen, S, Weitzman, E, Hellman, L. Synchronization of augmented luteinizing hormone secretion with sleep during puberty. N Engl J Med. 1972;287:582586.Google Scholar
Lee, JH, Miele, ME, Hicks, DJ, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996;88:17311737.Google Scholar
West, A, Vojta, PJ, Welch, DR, Weissman, BE. Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1). Genomics. 1998;54:145148.Google Scholar
Pasquier, J, Kamech, N, Lafont, AG, Vaudry, H, Rousseau, K, Dufour, S. Molecular evolution of GPCRs: kisspeptin/kisspeptin receptors. J Mol Endocrinol. 2014;52:T101T117.Google Scholar
Ohtaki, T, Shintani, Y, Honda, S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411:613617.Google Scholar
Liu, X, Lee, K, Herbison, AE. Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology. 2008;149:46054614.Google Scholar
Hrabovszky, E, Ciofi, P, Vida, B, et al. The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin-releasing hormone and neurokinin B neurons. Eur J Neurosci. 2010;31:19841998.Google Scholar
Uenoyama, Y, Inoue, N, Pheng, V, et al. Ultrastructural evidence of kisspeptin-gonadotrophin-releasing hormone (GnRH) interaction in the median eminence of female rats: implication of axo-axonal regulation of GnRH release. J Neuroendocrinol. 2011;23:863870.Google Scholar
Messager, S, Chatzidaki, EE, Ma, D, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA. 2005;102:17611766.Google Scholar
Lehman, MN, Coolen, LM, Goodman, RL. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology. 2010;151:34793489.Google Scholar
Skorupskaite, K, George, JT, Anderson, RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update. 2014;20:485500.Google Scholar
Topaloglu, AK, Semple, RK. Neurokinin B signalling in the human reproductive axis. Mol Cell Endocrinol. 2011;346:5764.Google Scholar
Marques, P, Skorupskaite, K, George, JT, et al. Physiology of GNRH and gonadotropin secretion. [Updated 2018 Jun 19]. In: Feingold, KR, Anawalt, B, Boyce, A, et al., eds. Endotext [Internet]. MDText.com, Inc.; 2000–. Available from: www.ncbi.nlm.nih.gov/books/NBK279070/.Google Scholar
Pinilla, L, Aguilar, E, Dieguez, C, Millar, RP, Tena-Sempere, M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92:12351316.Google Scholar
Ikegami, K, Minabe, S, Ieda, N, et al. Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones. J Neuroendocrinol. 2017:29.Google Scholar
Dhillo, W, Chaudhuri, O, Patterson, M, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary-gonadal axis in human males. J Clin Endocrinol Metab. 2005;90:66096615.Google Scholar
Gutierrez-Pascual, E, Martinez-Fuentes, AJ, Pinilla, L, Tena-Sempere, M, Malagon, MM, Castano, JP. Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretion. J Neuroendocrinol. 2007;19:521530.Google Scholar
Navarro, VM, Bosch, MA, Leon, S, et al. The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology. 2015;156:627637.Google Scholar
Han, SK, Gottsch, ML, Lee, KJ, et al. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci. 2005;25:1134911356.Google Scholar
de Roux, N, Genin, E, Carel, JC, Matsuda, F, Chaussain, JL, Milgrom, E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003;100:1097210976.CrossRefGoogle ScholarPubMed
Topaloglu, AK, Reimann, F, Guclu, M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009;41:354358.Google Scholar
Teles, MG, Bianco, SD, Brito, VN, et al. GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008;358:709715.Google Scholar
Silveira, LG, Noel, SD, Silveira-Neto, AP, et al. Mutations of the KISS1 gene in disorders of puberty. J Clin Endocrinol Metab. 2010;95:22762280.Google Scholar
Clarke, SA, Dhillo, WS. Kisspeptin across the human lifespan: evidence from animal studies and beyond. J Endocrinol. 2016;229:R83R98.Google Scholar
Comninos, AN, Dhillo, WS. Emerging roles of kisspeptin in sexual and emotional brain processing. Neuroendocrinology. 2018;106:195202.Google Scholar
Dudek, M, Ziarniak, K, Sliwowska, JH. Kisspeptin and metabolism: the brain and beyond. Front Endocrinol (Lausanne). 2018;9:145.Google Scholar
Navarro, VM, Gottsch, ML, Wu, M, et al. Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology. 2011;152:42654275.Google Scholar
Shibata, M, Friedman, RL, Ramaswamy, S, Plant, TM. Evidence that down regulation of hypothalamic KiSS-1 expression is involved in the negative feedback action of testosterone to regulate luteinising hormone secretion in the adult male rhesus monkey (Macaca mulatta). J Neuroendocrinol. 2007;19:432438.Google Scholar
Smith, JT, Dungan, HM, Stoll, EA, et al. Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology. 2005;146:29762984.Google Scholar
Rochira, V, Zirilli, L, Genazzani, AD, et al. Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback. Eur J Endocrinol. 2006;155:513522.Google Scholar
Raven, G, de Jong, FH, Kaufman, JM, de Ronde, W. In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion. J Clin Endocr. 2006;91:33243328.Google Scholar
Goodman, RL, Coolen, LM, Anderson, GM, et al. Evidence that dynorphin plays a major role in mediating progesterone negative feedback on gonadotropin-releasing hormone neurons in sheep. Endocrinology. 2004;145:29592967.Google Scholar
Boutari, C, Pappas, PD, Mintziori, G, et al. The effect of underweight on female and male reproduction. Metabolism. 2020;107:154229.Google Scholar
Mintziori, G, Nigdelis, MP, Mathew, H, Mousiolis, A, Goulis, DG, Mantzoros, CS. The effect of excess body fat on female and male reproduction. Metabolism. 2020;107:154193.Google Scholar
Jahan, S, Bibi, R, Ahmed, S, Kafeel, S. Leptin levels in infertile males. J Coll Physicians Surg Pak. 2014;21:393397.Google Scholar
Quennell, JH, Mulligan, AC, Tups, A, et al. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology. 2009;150:28052812.Google Scholar
Smith, JT, Acohido, BV, Clifton, DK, Steiner, RA. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J Neuroendocrinol. 2006;4:298303.Google Scholar
Yeo, SH, Colledge, WH. The role of Kiss1 neurons as integrators of endocrine, metabolic, and environmental factors in the hypothalamic-pituitary-gonadal axis. Front Endocrinol (Lausanne). 2018;9:188.Google Scholar
Farooqi, IS, O’Rahilly, S. Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr. 2009;89:980S984S.Google Scholar
DiVall, SA, Radovick, S, Wolfe, A. Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin. Mol Cell Endocrinol. 2007;270:6472.Google Scholar
Zhen, S, Zakaria, M, Wolfe, A, Radovick, S. Regulation of gonadotropin-releasing hormone (GnRH) gene expression by insulin-like growth factor I in a cultured GnRHexpressing neuronal cell line. Mol Endocrinol. 1997;11:11451155.Google Scholar
Farkas, I, Vastagh, C, Sárvári, M, Liposits, Z. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH) neurons in an estrous cycle and endocannabinoid signaling dependent manner. PLoS ONE. 2013;8:e78178.Google Scholar
Oakley, AE, Breen, KM, Clarke, IJ, Karsch, FJ, Wagenmaker, ER, Tilbrook, AJ. Cortisol reduces gonadotropin-releasing hormone pulse frequency in follicular phase ewes: influence of ovarian steroids. Endocrinology. 2009;150:341349.Google Scholar
Kinsey-Jones, JS, Li, XF, Knox, AM, et al. Down-regulation of hypothalamic kisspeptin and its receptor, Kiss1r, mRNA expression is associated with stress-induced suppression of luteinising hormone secretion in the female rat. J Neuroendocrinol. 2009;21:2029.Google Scholar
Ducret, E, Anderson, GM, Herbison, AE. RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology. 2009;150:27992804.Google Scholar
Liu, X, Herbison, AE. Kisspeptin regulation of neuronal activity throughout the central nervous system. Endocrinol Metabol. 2016;31:193205.Google Scholar
Cheng, CK, Leung, PC. Molecular biology of gonadotropin releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr Rev. 2005;26:283306.Google Scholar
Kakar, SS. Molecular structure of the human gonadotropin releasing hormone receptor gene. Eur J Endocrinol. 1997;137:183192.Google Scholar
Grosse, R, Schmid, A, Schoneberg, T, et al. Gonadotropin-releasing hormone receptor initiates multiple signaling pathways by exclusively coupling to Gq/11 proteins. J Biol Chem. 2000;275:91939200.Google Scholar
Stojilkovic, SS, Reinhart, J, Catt, KJ. Gonadotropin-releasing hormone receptors: structure and signal transduction pathways. Endocr Rev. 1994;15:462499.Google Scholar
Perrett, RM, McArdle, CA. Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network. Front Endocrinol (Lausanne). 2013;4:180.Google Scholar
Padmanabhan, V, McFadden, K, Mauger, DT, Karsch, FJ, Midgley, AR Jr. Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion. Endocrinology. 1997;138:424432.Google Scholar
Kaiser, UB, Jakubowiak, A, Steinberger, A, Chin, WW. Differential effects of gonadotropin-releasing hormone (GnRH) pulse frequency on gonadotropin subunit and GnRH receptor messenger ribonucleic acid levels in vitro. Endocrinology. 1997;138:12241231.Google Scholar
Tsutsumi, M, Laws, SC, Rodic, V, Sealfon, SC. Translational regulation of the gonadotropin-releasing hormone receptor in T3–1 cells. Endocrinology. 1995;136:11281136.Google Scholar
McArdle, CA, Franklin, J, Green, L, Hislop, JN. Signaling, cycling and desensitization of gonadotropin-releasing hormone receptors. J Endocrinol. 2002;173:111.Google Scholar
Harris, D, Chuderland, D, Bonfil, D, Kraus, S, Seger, R, Naor, Z. Extracellular signal-regulated kinase and c-Src, but not Jun N-terminal kinase, are involved in basal and gonadotropin releasing hormone-stimulated activity of the glycoprotein hormone-subunit promoter. Endocrinology. 2003;144:612622.Google Scholar
Lanciotti, L, Cofini, M, Leonardi, A, Penta, L, Esposito, S. Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life. Front Endocrinol. 2018;9:410.Google Scholar
O’Donnell, L, Stanton, P, de Kretser, DM. Endocrinology of the male reproductive system and spermatogenesis. [Updated 2017 Jan 11]. In: Feingold, KR, Anawalt, B, Boyce, A, et al., eds. Endotext [Internet]. MDText.com, Inc.; 2000–. Available from: www.ncbi.nlm.nih.gov/books/NBK279031/.Google Scholar
Pitteloud, N, Dwyer, AA, DeCruz, S, et al. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab. 2008;93:784791.Google Scholar
Sheckter, CB, Matsumoto, AM, Bremner, WJ. Testosterone administration inhibits gonadotropin secretion by an effect directly on the human pituitary. J Clin Endocrinol Metab. 1989;68:397401.Google Scholar
Hayes, FJ, DeCruz, S, Seminara, SB, Boepple, PA, Crowley, WF Jr. Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion. J Clin Endocrinol Metab. 2001;86:5358.Google Scholar
Rochira, V, Madeo, B, Diazzi, C, Zirilli, L, Daniele, S, Carani, C. Estrogens and male reproduction. [Updated 2016 Nov 24]. In: Feingold, KR et al., eds. Endotext [Internet]. MDText.com, Inc.; 2000–. Available from www.ncbi.nlm.nih.gov/books/NBK278933/.Google Scholar
de Kretser, DM, Robertson, DM. The isolation and physiology of inhibin and related proteins. Biol Reprod. 1989;40:3347.Google Scholar
Iliadou, PK, Tsametis, C, Kaprara, A, Papadimas, I, Goulis, DG. The Sertoli cell: novel clinical potentiality. Hormones (Athens). 2015;14:504514.Google Scholar
Namwanje, M, Brown, CW. Activins and inhibins: roles in development, physiology, and disease. Cold Spring Harb Perspect Biol. 2016;8:a021881.Google Scholar
Burger, LL, Dalkin, AC, Aylor, KW, Haisenleder, DJ, Marshall, JC. GnRH pulse frequency modulation of gonadotropin subunit gene transcription in normal gonadotropes-assessment by primary transcript assay provides evidence for roles of GnRH and follistatin. Endocrinology. 2002;143:32433249.Google Scholar
Kaiser, UB, Lee, BL, Carroll, RS, Unabia, G, Chin, WW, Childs, GV. Follistatin gene expression in the pituitary: localization in gonadotropes and folliculostellate cells in diestrous rats. Endocrinology. 1992;130:30483056.Google Scholar
Tsutsui, K, Saigoh, E, Ukena, K, et al. A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Commun. 2000;275:661667.Google Scholar
Tsutsui, K, Ukena, K. Hypothalamic LPXRF-amide peptides in vertebrates: identification, localization and hypophysiotropic activity. Peptides. 2006;27:11211129.Google Scholar
Ubuka, T, Morgan, K, Pawson, AJ, et al. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS ONE. 2009;4:e8400.Google Scholar
Hu, KL, Chang, HM, Li, R, Yu, Y, Qiao, J. Regulation of LH secretion by RFRP-3: from the hypothalamus to the pituitary. Front Neuroendocrinol. 2019;52:1221.Google Scholar
Hinuma, S, Shintani, Y, Fukusumi, S, et al. New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat Cell Biol. 2000;2:703708.Google Scholar
Tsutsui, K, Ubuka, T, Son, YL, Bentley, GE, Kriegsfeld, LJ. Contribution of GnIH research to the progress of reproductive neuroendocrinology. Front Endocrinol (Lausanne). 2015; 6:179.Google Scholar
George, JT, Hendrikse, M, Veldhuis, JD, Clarke, IJ, Anderson, RA, Millar, RP Effect of gonadotropin-inhibitory hormone on luteinizing hormone secretion in humans. Clin. Endocrinol. 2017;86:731738.Google Scholar
Anderson, RC, Newton, CL, Anderson, RA, Millar, RP. Gonadotropins and their analogs: current and potential clinical applications. Endocr Rev. 2018;39:911937.Google Scholar
Jiang, X, Liu, H, Chen, X, et al. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc Natl Acad Sci USA. 2012;109:1249112496.Google Scholar
Hsueh, AJ, He, J. Gonadotropins and their receptors: coevolution, genetic variants, receptor imaging, and functional antagonists. Biol Reprod. 2018;99:312.Google Scholar
Teerds, KJ, Huhtaniemi, IT. Morphological and functional maturation of Leydig cells: from rodent models to primates. Hum Reprod Update. 2015;21:310328.Google Scholar
Zirkin, BR, Papadopoulos, V. Leydig cells: formation, function, and regulation. Biol Reprod. 2018;99:101111.Google Scholar
Wang, Y, Chen, F, Ye, L, Zirkin, B, Chen, H. Steroidogenesis in Leydig cells: effects of aging and environmental factors. Reproduction. 2017;154:R111R122.Google Scholar
Casarini, L, Santi, D, Brigante, G, Simoni, M. Two hormones for one receptor: evolution, biochemistry, actions, and pathophysiology of LH and hCG. Endocr Rev. 2018;39:549592.Google Scholar
Santi, D, Crépieux, P, Reiter, E, et al. Follicle-stimulating hormone (FSH) action on spermatogenesis: a focus on physiological and therapeutic roles. J Clin Med. 2020;9:1014.Google Scholar
Ruwanpura, SM, McLachlan, RI, Meachem, SJ. Hormonal regulation of male germ cell development. J Endocrinol. 2010;205:117131.Google Scholar
Xu, HY, Zhang, HX, Xiao, Z, Qiao, J, Li, R. Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J Androl. 2019;21:109114.Google ScholarPubMed
Meachem, SJ, Nieschlag, E, Simoni, M. Inhibin B in male reproduction: pathophysiology and clinical relevance. Eur J Endocrinol. 2001;145:561571.Google Scholar
Huhtaniemi, I. A short evolutionary history of FSH-stimulated spermatogenesis. Hormones (Athens). 2015;14:468478.Google Scholar
Griffin, J, Wilson, JD, Snyder, PJ, Matsumoto, AM, Martin, KA. Male reproductive physiology. In: Post, TW, ed. UpToDate. UpToDate; 2013.Google Scholar
Nieschlag, E, Behre, HM, Nieschlag, S. Andrology: Male Reproductive Health and Dysfunction. 3rd ed. Springer-Verlag; 2010.Google Scholar
Matsumoto, A, Bremner, W. Male hypogonadism. In: Melmed, S, Polonsky, K, Larsen, P, Kroneneberg, H, eds. Williams Textbook of Endocrinology. 12th ed. Saunders; 2011:709755.Google Scholar
Kanakis, GA, Goulis, DG. Classification and epidemiology of hypogonadism. In: Simoni, M, Huhtaniemi, I, eds. Endocrinology of the Testis and Male Reproduction. Springer; 2017:123.Google Scholar
Miller, WL, Auchus, RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32:81151.Google Scholar
Miller, WL. StAR search: what we know about how the steroidogenic acute regulatory protein mediates mitochondrial cholesterol import. Mol Endocrinol. 2007;21:589601.Google Scholar
Tuckey, RC, Cameron, KJ. Catalytic properties of cytochrome P-450scc purified from the human placenta: comparison to bovine cytochrome P-450scc. Biochim Biophys Acta. 1993;1163:185194.Google Scholar
Kim, CJ, Lin, L, Huang, N, et al. Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc. J Clin Endocrinol Metabol. 2008;93:696702.Google Scholar
Chung, BC, Picado-Leonard, J, Haniu, M, et al. Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Nat Acad Sci USA. 1987;84:407411.Google Scholar
Lachance, Y, Luu-The, V, Labrie, C, et al. Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells. J Biol Chem. 1990;265:2046920475.Google Scholar
Flück, CE, Miller, WL, Auchus, RJ. The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway. J Clin Endocrinol Metabol. 2003;88:37623766.Google Scholar
Labrie, F, Luu-The, V, Lin, SX, et al. The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology. Steroids. 1997;62:148158.Google Scholar
Manna, PR, Stetson, CL, Slominski, AT, Pruitt, K. Role of the steroidogenic acute regulatory protein in health and disease. Endocrine. 2016;51:721.Google Scholar
Winters, SJ, Troen, P. Testosterone and estradiol are co-secreted episodically by the human testis. J Clin Inv. 1986;78:870873.Google Scholar
Plymate, SR, Tenover, JS, Bremner, WJ. Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. J Androl. 1989;10:366371.Google Scholar
Sheckter, CB, Matsumoto, AM, Bremner, WJ. Testosterone administration inhibits gonadotropin secretion by an effect directly on the human pituitary. J Clin Endocrinol Metabol. 1989;68:397401.Google Scholar
Morishima, A, Grumbach, MM, Simpson, ER, Fisher, C, Qin, K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metabol. 1995;80:36893698.Google Scholar
Sansone, A, Kliesch, S, Isidori, AM, Schlatt, S. AMH and INSL3 in testicular and extragonadal pathophysiology: what do we know? Andrology. 2019;7:131138.Google Scholar
Bay, K, Hartung, S, Ivell, R, et al. Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metabol. 2005;90:34103438.Google Scholar
Ferlin, A, Garolla, A, Rigon, F, Rasi Caldogno, L, Lenzi, A, Foresta, C. Changes in serum insulin-like factor 3 during normal male puberty. J Clin Endocrinol Metabol. 2006;91:34263431.Google Scholar
de Kretser, DM, Buzzard, JJ, Okuma, Y, et al. The role of activin, follistatin and inhibin in testicular physiology. Mol Cell Endocrinol. 2004;225:5764.Google Scholar
Boepple, PA, Hayes, FJ, Dwyer, AA, et al. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function. J Clin Endocrinol Metabol. 2008;93:18091814.Google Scholar
Anawalt, BD, Bebb, RA, Matsumoto, AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J Clin Endocrinol Metabol. 1996;81:33413335.Google Scholar
Jamin, SP, Arango, NA, Mishina, Y, Hanks, MC, Behringer, RR. Genetic studies of the AMH/MIS signaling pathway for Müllerian duct regression. Mol Cell Endocrinol. 2003;211:1519.Google Scholar
Sofikitis, N, Giotitsas, N, Tsounapi, P, Baltogiannis, D, Giannakis, D, Pardalidis, N. Hormonal regulation of spermatogenesis and spermiogenesis. J Steroid Biochem Mol Biol. 2008;109:323330.Google Scholar
Hammond, GL. Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod. 2011:85:431441.Google Scholar
Manni, A, Pardridge, WM, Cefalu, W, et al. Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metabol. 1985;61:705710.Google Scholar
Giton, F, Fiet, J, Guéchot, J, et al. Serum bioavailable testosterone: assayed or calculated? Clin Chem. 2006;52:474481.Google Scholar
Goldman, AL, Bhasin, S, Wu, FCW, Krishna, M, Matsumoto, AM, Jasuja, R. A reappraisal of testosterone’s binding in circulation: physiological and clinical implications. Endocr Rev. 2017;38:302324.Google Scholar
Joseph, DR. Structure, function, and regulation of androgen-binding protein/sex hormone-binding globulin. Vitamins Hormones. 1994;49:197280.Google Scholar
Stone, J, Folkerd, E, Doody, D, et al. Familial correlations in postmenopausal serum concentrations of sex steroid hormones and other mitogens: a twins and sisters study. J Clin Endocrinol Metabol. 2009:94:47934800.Google Scholar
Bhasin, S, Cunningham, GR, Hayes, FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metabol. 2018;103:130.Google Scholar
de Ronde, W, van der Schouw, YT, Pols, HAP, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem. 2006;52:17771784.Google Scholar
Schiffer, L, Arlt, W, Storbeck, K-H. Intracrine androgen biosynthesis, metabolism and action revisited. Mol Cell Endocrinol. 2018:465:426.Google Scholar
Imperato-McGinley, J, Zhu, Y-S. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198:5159.Google Scholar
Bertelloni, S, Baldinotti, F, Russo, G, et al. 5α-reductase-2 deficiency: clinical findings, endocrine pitfalls, and genetic features in a large Italian cohort. Sex Develop. 2016;10:2836.Google Scholar
Swerdloff, RS, Dudley, RE, Page, ST, Wang, C, Salameh, WA. Dihydrotestosterone: biochemistry, physiology, and clinical implications of elevated blood levels. Endocr Rev. 2017:38:220254.Google Scholar
Wilson, EM, French, FS. Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem. 1976;251:56205629.Google Scholar
Lombardi, G, Zarrilli, S, Colao, A, et al. Estrogens and health in males. Mol Cell Endocrinol. 2001;178:5155.Google Scholar
Bélanger, A, Pelletier, G, Labrie, F, Barbier, O, Chouinard, S. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metabol. 2003;14:473479.Google Scholar
Rey, RA, Grinspon, RP, Gottlieb, S, et al. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach. Andrology. 2013;1:316.Google Scholar
Shukla, GC, Plaga, AR, Shankar, E, Gupta, S. Androgen receptor-related diseases: what do we know? Andrology. 2016;4:366381.Google Scholar
Lee, DK, Chang, C. Molecular communication between androgen receptor and general transcription machinery. J Steroid Biochem Mol Biol. 2003;84:4149.Google Scholar
Brinkmann, AO, Faber, PW, van Rooij, HC, et al. The human androgen receptor: domain structure, genomic organization and regulation of expression. J Steroid Biochem. 1989;34:307310.Google Scholar
Zitzmann, M. Pharmacogenetics of testosterone replacement therapy. Pharmacogenomics. 2009;10:13411349.Google Scholar
Foradori, CD, Weiser, MJ, Handa, RJ. Non-genomic actions of androgens. Front Neuroendocrinol. 2008;29:169181.Google Scholar
Gorczynska, E, Handelsman, DJ. Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells. Endocrinology. 1995;136:20522059.Google Scholar
Cheng, J, Watkins, SC, Walker, WH. Testosterone activates mitogen-activated protein kinase via Src kinase and the epidermal growth factor receptor in Sertoli cells. Endocrinology. 2007;148:20662074.Google Scholar
Hammes, A, Andreassen, TK, Spoelgen, R, et al. Role of endocytosis in cellular uptake of sex steroids. Cell. 2005;122:751762.Google Scholar
Tapanainen, J, Kellokumpu-Lehtinen, P, Pelliniemi, L, Huhtaniemi, I. Age-related changes in endogenous steroids of human fetal testis during early and midpregnancy. J Clin Endocrinol Metabol. 1981;52:98102.Google Scholar
Grumbach, MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metabol. 2005;90:31223127.Google Scholar
Patton, GC, Viner, R. Pubertal transitions in health. Lancet. 2007;369:11301139.Google Scholar
Gray, A, Feldman, HA, McKinlay, JB, Longcope, C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991;73:10161025.Google Scholar
Andersson, AM, Toppari, J, Haavisto, AM, et al. Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metabol. 1998;83:675681.Google Scholar
Grinspon, RP, Rey, RA. New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker. Arq Brasil Endocrinol Metabol. 2011;55:512519.Google Scholar

References

Balhorn, R. A model for the structure of chromatin in mammalian sperm. J Cell Biol. 1982;93:298305.Google Scholar
Hud, NV, Allen, MJ, Downing, KH, Lee, J, Balhorn, R. Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy. Biochem Biophys Res Commun. 1993;193:13471354.Google Scholar
Hud, NV, Downing, KH, Balhorn, R. A constant radius of curvature model for the organization of DNA in toroidal condensates. Proc Natl Acad Sci U S A. 1995;92:35813585.Google Scholar
Smith, MM. Histone structure and function. Curr Opin Cell Biol. 1991;3:429437.Google Scholar
Hud, NV, Downing, KH. Cryoelectron microscopy of lambda phage DNA condensates in vitreous ice: the fine structure of DNA toroids. Proc Natl Acad Sci U S A. 2001;98:1492514930.Google Scholar
Conwell, CC, Vilfan, ID, Hud, NV. Controlling the size of nanoscale toroidal DNA condensates with static curvature and ionic strength. Proc Natl Acad Sci U S A. 2003;100:92969301.Google Scholar
Ward, WS, Partin, AW, Coffey, DS. DNA loop domains in mammalian spermatozoa. Chromosoma. 1989;98:153159.Google Scholar
Nadel, B, de Lara, J, Finkernagel, SW, Ward, WS. Cell-specific organization of the 5S ribosomal RNA gene cluster DNA loop domains in spermatozoa and somatic cells. Biol Reprod. 1995;53:12221228.Google Scholar
Pardoll, DM, Vogelstein, B, Coffey, DS. A fixed site of DNA replication in eucaryotic cells. Cell. 1980;19:527536.Google Scholar
Vogelstein, B, Pardoll, DM, Coffey, DS. Supercoiled loops and eucaryotic DNA replication. Cell. 1980;22:7985.Google Scholar
Paulson, JR, Laemmli, UK. The structure of histone-depleted metaphase chromosomes. Cell. 1977;12:817828.Google Scholar
Earnshaw, WC, Halligan, B, Cooke, CA, Heck, MM, Liu, LF. Topoisomerase II is a structural component of mitotic chromosome scaffolds. J Cell Biol. 1985;100:17061715.Google Scholar
Earnshaw, WC, Heck, MM. Localization of topoisomerase II in mitotic chromosomes. J Cell Biol. 1985;100:17161725.Google Scholar
Li, TK, Chen, AY, Yu, C, Mao, Y, Wang, H, Liu, LF. Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress. Genes Dev. 1999;13:15531560.Google Scholar
Ward, WS. Chromosome organization in mammalian sperm nuclei. In: Barratt, CL, de Jong, JH, Mortimer, D, Parinaud, J, eds. Genetics of Human Male Fertility. Editions E.D.K.; 1997:147163.Google Scholar
Sotolongo, B, Lino, E, Ward, WS. Ability of hamster spermatozoa to digest their own DNA. Biol Reprod. 2003;69:20292035.Google Scholar
Ward, WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod. 2010;16:3036.Google Scholar
Shaman, JA, Yamauchi, Y, Ward, WS. Sperm DNA fragmentation: awakening the sleeping genome. Biochem Soc Trans. 2007;35:626628.Google Scholar
Boaz, SM, Dominguez, KM, Shaman, JA, Ward, WS. Mouse spermatozoa contain a nuclease that is activated by pretreatment with EGTA and subsequent calcium incubation. J Cell Biochem. 2008;103:16361645.Google Scholar
Gawecka, JE, Boaz, S, Kasperson, K, Nguyen, H, Evenson, DP, Ward, WS. Luminal fluid of epididymis and vas deferens contributes to sperm chromatin fragmentation. Hum Reprod. 2015;30:27252736.Google Scholar
Shaman, JA, Prisztoka, R, Ward, WS. Topoisomerase IIB and an extracellular nuclease interact to digest sperm DNA in an apoptotic-like manner. Biol Reprod. 2006;75:741748.Google Scholar
Liu, LF, Rowe, TC, Yang, L, Tewey, KM, Chen, GL. Cleavage of DNA by mammalian DNA topoisomerase II. J Biol Chem. 1983;258:1536515370.Google Scholar
Sotolongo, B, Huang, TF, Isenberger, E, Ward, WS. An endogenous nuclease in hamster, mouse and human spermatozoa cleaves DNA into loop-sized fragments. J Androl. 2005;26:272280.Google Scholar
Lagarkova, MA, Iarovaia, OV, Razin, SV. Large-scale fragmentation of mammalian DNA in the course of apoptosis proceeds via excision of chromosomal DNA loops and their oligomers. J Biol Chem. 1995;270:2023920241.Google Scholar
Solovyan, VT, Bezvenyuk, ZA, Salminen, A, Austin, CA, Courtney, MJ. The role of topoisomerase II in the excision of DNA loop domains during apoptosis. J Biol Chem. 2002;277:2145821467.Google Scholar
Widlak, P, Garrard, WT. Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. J Cell Biochem. 2005;94:10781087.Google Scholar
Brykczynska, U, Hisano, M, Erkek, S, et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol. 2010;17:679687.Google Scholar
Hammoud, SS, Nix, DA, Zhang, H, Purwar, J, Carrell, DT, Cairns, BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460:473478.Google Scholar
Arpanahi, A, Brinkworth, M, Iles, D, et al. Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res. 2009;19:13381349.Google Scholar

References

Revenig, L, Leung, A, Hsiao, W. Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility. Transl Androl Urol. 2014;3(1):4149. doi:10.3978/j.issn.2223-4683.2014.02.02Google Scholar
Althof, SE. Prevalence, characteristics and implications of premature ejaculation/rapid ejaculation. J Urol. 2006;175(3 Pt 1):842848. doi:10.1016/S0022-5347(05)00341-1Google Scholar
Giuliano, F. Neurophysiology of erection and ejaculation. J Sex Med. 2011;8 (Suppl 4):310315. doi:10.1111/j.1743-6109.2011.02450.xGoogle Scholar
Abdel-Hamid, IA, Ali, OI. Delayed ejaculation: pathophysiology, diagnosis, and treatment. World J Mens Health. 2018;36(1):2240. doi:10.5534/wjmh.17051Google Scholar
Giuliano, F, Clement, P. Neuroanatomy and physiology of ejaculation. Annu Rev Sex Res. 2005;16:190216.Google Scholar
Lipshultz, LI, Howards, SS, Niederberger, CS. Infertility in the Male. 4th ed. Cambridge University Press; 2009.Google Scholar
Hafez, ESE. Human Semen and Fertility Regulation in Men. Mosby; 1976.Google Scholar
Vaucher, L, Bolyakov, A, Paduch, DA. Evolving techniques to evaluate ejaculatory function. Curr Opin Urol. 2009;19(6):606614. doi:10.1097/MOU.0b013e3283318ee2Google Scholar
Yang, CC, Bradley, WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve. 1998;21(4):514518. doi:10.1002/(sici)1097-4598(199804)21:4<514::aid-mus10>3.0.co;2-xGoogle Scholar
Wieder, JA, Brackett, NL, Lynne, CM, Green, JT, Aballa, TC. Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries. Urology. 2000;55(6):915917. doi:10.1016/s0090-4295(99)00608-1Google Scholar
Clement, P, Giuliano, F. Physiology and pharmacology of ejaculation. Basic Clin Pharmacol Toxicol. 2016;119(Suppl 3):1825. doi:10.1111/bcpt.12546Google Scholar
Educational Committee of the ESSM. The ESSM Manual of Sexual Medicine. 2nd updated ed: Medix; 2015.Google Scholar
David Prologo, J, Snyder, LL, Cherullo, E, Passalacqua, M, Pirasteh, A, Corn, D. Percutaneous CT-guided cryoablation of the dorsal penile nerve for treatment of symptomatic premature ejaculation. J Vasc Interv Radiol. 2013;24(2):214219. doi:10.1016/j.jvir.2012.09.015Google Scholar
Serefoglu, EC, McMahon, CG, Waldinger, MD, et al. An evidence-based unified definition of lifelong and acquired premature ejaculation: report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. J Sex Med. 2014;11(6):14231441. doi:10.1111/jsm.12524Google Scholar
Patrick, DL, Althof, SE, Pryor, JL, et al. Premature ejaculation: an observational study of men and their partners. J Sex Med. 2005;2(3):358367. doi:10.1111/j.1743-6109.2005.20353.xGoogle Scholar
Lorentzen, SS, Papoutsakis, C, Myers, EF, Thoresen, L. Adopting nutrition care process terminology at the national level: the Norwegian experience in evaluating compatibility with international statistical classification of diseases and related health problems, 10th revision, and the existing Norwegian coding system. J Acad Nutr Diet. 2019;119(3):375393. doi:10.1016/j.jand.2018.02.006Google Scholar
Parnham, A, Serefoglu, EC. Classification and definition of premature ejaculation. Transl Androl Urol. 2016;5(4):416423. doi:10.21037/tau.2016.05.16Google Scholar
Bernard, S. Premature ejaculation: a review of 1130 cases. J Urol. 1943:374379.Google Scholar
Waldinger, MD. The pathophysiology of lifelong premature ejaculation. Transl Androl Urol. 2016;5(4):424433. doi:10.21037/tau.2016.06.04Google Scholar
Gao, J, Zhang, X, Su, P, et al. Prevalence and factors associated with the complaint of premature ejaculation and the four premature ejaculation syndromes: a large observational study in China. J Sex Med. 2013;10(7):18741881. doi:10.1111/jsm.12180Google Scholar
Pereira-Lourenço, M, Brito, DVE, Pereira, BJ. Premature ejaculation: from physiology to treatment. J Family Reprod Health. 2019;13(3):120131.Google Scholar
Lindau, ST, Schumm, LP, Laumann, EO, Levinson, W, O’Muircheartaigh, CA, Waite, LJ. A study of sexuality and health among older adults in the United States. N Engl J Med. 2007;357(8):762774. doi:10.1056/NEJMoa067423Google Scholar
Oztürk, M, Koca, O, Tüken, M, Keleş, MO, Ilktaç, A, Karaman, MI. Hormonal evaluation in premature ejaculation. Urol Int. 2012;88(4):454458. doi:10.1159/000336137Google Scholar
Patrick, DL, Giuliano, F, Ho, KF, Gagnon, DD, McNulty, P, Rothman, M. The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice. BJU Int. 2009;103(3):358364. doi:10.1111/j.1464-410X.2008.08041.xGoogle Scholar
Barnes, T, Eardley, I. Premature ejaculation: the scope of the problem. J Sex Marital Ther. 2007;33(2):151170. doi:10.1080/00926230601098472Google Scholar
Frühauf, S, Gerger, H, Schmidt, HM, Munder, T, Barth, J. Efficacy of psychological interventions for sexual dysfunction: a systematic review and meta-analysis. Arch Sex Behav. 2013;42(6):915933. doi:10.1007/s10508-012-0062-0Google Scholar
Melnik, T, Althof, S, Atallah, AN, Puga, ME, Glina, S, Riera, R. Psychosocial interventions for premature ejaculation. Cochrane Database Syst Rev. 2011;(8):CD008195. doi:10.1002/14651858.CD008195.pub2Google Scholar
Althof, SE, McMahon, CG, Waldinger, MD, et al. An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med. 2014;2(2):6090. doi:10.1002/sm2.28Google Scholar
Hershlag, A, Schiff, SF, DeCherney, AH. Retrograde ejaculation. Hum Reprod. 1991;6(2):255258. doi:10.1093/oxfordjournals.humrep.a137317Google Scholar
Mano, R, Di Natale, R, Sheinfeld, J. Current controversies on the role of retroperitoneal lymphadenectomy for testicular cancer. Urol Oncol. 2019;37(3):209218. doi:10.1016/j.urolonc.2018.09.009Google Scholar
Gaunay, G, Nagler, HM, Stember, DS. Reproductive sequelae of diabetes in male patients. Endocrinol Metab Clin North Am. 2013;42(4):899914. doi:10.1016/j.ecl.2013.07.003Google Scholar
Dunsmuir, WD, Holmes, SA. The aetiology and management of erectile, ejaculatory, and fertility problems in men with diabetes mellitus. Diabet Med. 1996;13(8):700708. doi:10.1002/(SICI)1096-9136(199608)13:8<700::AID-DIA174>3.0.CO;2-8Google Scholar
Hellstrom, WJ, Sikka, SC. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol. 2006;176(4 Pt 1):15291533. doi:10.1016/j.juro.2006.06.004Google Scholar
Hisasue, S, Furuya, R, Itoh, N, Kobayashi, K, Furuya, S, Tsukamoto, T. Ejaculatory disorder caused by alpha-1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int J Urol. 2006;13(10):13111316. doi:10.1111/j.1442-2042.2006.01535.xGoogle Scholar
Gacci, M, Ficarra, V, Sebastianelli, A, et al. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. J Sex Med. 2014;11(6):15541566. doi:10.1111/jsm.12525Google Scholar
DeLay, KJ, Nutt, M, McVary, KT. Ejaculatory dysfunction in the treatment of lower urinary tract symptoms. Transl Androl Urol. 2016;5(4):450459. doi:10.21037/tau.2016.06.06Google Scholar
Rassweiler, J, Teber, D, Kuntz, R, Hofmann, R. Complications of transurethral resection of the prostate (TURP): incidence, management, and prevention. Eur Urol. 2006;50(5):969979; discussion 980. doi:10.1016/j.eururo.2005.12.042Google Scholar
Cornu, JN, Ahyai, S, Bachmann, A, et al. A systematic review and meta-analysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic obstruction: an update. Eur Urol. 2015;67(6):10661096. doi:10.1016/j.eururo.2014.06.017Google Scholar
Briganti, A, Naspro, R, Gallina, A, et al. Impact on sexual function of holmium laser enucleation versus transurethral resection of the prostate: results of a prospective, 2-center, randomized trial. J Urol. 2006;175(5):18171821. doi:10.1016/S0022-5347(05)00983-3Google Scholar
Marra, G, Sturch, P, Oderda, M, Tabatabaei, S, Muir, G, Gontero, P. Systematic review of lower urinary tract symptoms/benign prostatic hyperplasia surgical treatments on men’s ejaculatory function: time for a bespoke approach? Int J Urol. 2016;23(1):2235. doi:10.1111/iju.12866Google Scholar
Lebdai, S, Chevrot, A, Doizi, S, et al. Do patients have to choose between ejaculation and miction? A systematic review about ejaculation preservation technics for benign prostatic obstruction surgical treatment. World J Urol. 2019;37(2):299308. doi:10.1007/s00345-018-2368-6Google Scholar
Gil-Vernet, JM, Alvarez-Vijande, R, Gil-Vernet, A. Ejaculation in men: a dynamic endorectal ultrasonographical study. Br J Urol. 1994;73(4):442448. doi:10.1111/j.1464-410x.1994.tb07612.xGoogle Scholar
Ronzoni, G, De Vecchis, M. Preservation of anterograde ejaculation after transurethral resection of both the prostate and bladder neck. Br J Urol. 1998;81(6):830833. doi:10.1046/j.1464-410x.1998.00658.xGoogle Scholar
Alloussi, SH, Lang, C, Eichel, R, Alloussi, S. Ejaculation-preserving transurethral resection of prostate and bladder neck: short- and long-term results of a new innovative resection technique. J Endourol. 2014;28(1):8489. doi:10.1089/end.2013.0093Google Scholar
Gilling, P, Barber, N, Bidair, M, et al. WATER: a double-blind, randomized, controlled trial of Aquablation. J Urol. 2018;199(5):12521261. doi:10.1016/j.juro.2017.12.065Google Scholar
Kamischke, A, Nieschlag, E. Update on medical treatment of ejaculatory disorders. Int J Androl. 2002;25(6):333344. doi:10.1046/j.1365-2605.2002.00379.xGoogle Scholar
Jefferys, A, Siassakos, D, Wardle, P. The management of retrograde ejaculation: a systematic review and update. Fertil Steril. 2012;97(2):306312. doi:10.1016/j.fertnstert.2011.11.019Google Scholar
Brackett, NL, Ibrahim, E, Iremashvili, V, Aballa, TC, Lynne, CM. Treatment for ejaculatory dysfunction in men with spinal cord injury: an 18-year single center experience. J Urol. 2010;183(6):23042308. doi:10.1016/j.juro.2010.02.018Google Scholar
Brackett, NL. Semen retrieval by penile vibratory stimulation in men with spinal cord injury. Hum Reprod Update. 1999;5(3):216222. doi:10.1093/humupd/5.3.216Google Scholar
Kathiresan, AS, Ibrahim, E, Aballa, TC, et al. Comparison of in vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries. Fertil Steril. 2011;96(3):562566. doi:10.1016/j.fertnstert.2011.06.078Google Scholar

References

Krausz, C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25:271285.Google Scholar
Watson, JD, Crick, FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171:737738.Google Scholar
Jacobs, PA, Strong, JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959;183:302303.Google Scholar
Lander, ES, Linton, LM, Birren, B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860921.Google Scholar
Tiepolo, L, Zuffardi, O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet. 1976;34:119124.Google Scholar
Chillon, M, Casals, T, Mercier, B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995;332:14751480.Google Scholar
Aston, KI. Genetic susceptibility to male infertility: news from genome-wide association studies. Andrology. 2014;2:315321.Google Scholar
Tuttelmann, F, Rajpert-De Meyts, E, Nieschlag, E, Simoni, M. Gene polymorphisms and male infertility – a meta-analysis and literature review. Reprod Biomed Online. 2007;15:643658.Google Scholar
Aston, KI, Carrell, DT. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl. 2009;30:711725.Google Scholar
Aston, KI, Conrad, DF. A review of genome-wide approaches to study the genetic basis for spermatogenic defects. Methods Mol Biol. 2013;927:397410.Google Scholar
Fruhmesser, A, Vogt, PH, Zimmer, J, et al. (2013) Single nucleotide polymorphism array analysis in men with idiopathic azoospermia or oligoasthenozoospermia syndrome. Fertil Steril. 100:8187.Google Scholar
Hu, Z, Xia, Y, Guo, X, et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nature Genetics. 2012;44:183186.Google Scholar
Krausz, C, Giachini, C, Lo Giacco, D, et al. High resolution X chromosome-specific array-CGH detects new CNVs in infertile males. PLoS ONE. 2012;7:e44887.Google Scholar
Stouffs, K, Vandermaelen, D, Massart, A, et al. Array comparative genomic hybridization in male infertility. Hum Reprod. 2012;27:921929.Google Scholar
Dam, AH, Koscinski, I, Kremer, JA, et al. Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am J Hum Genet. 2007;81:813820.Google Scholar
Koscinski, I, Elinati, E, Fossard, C, et al. DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Gen. 2011;88:344350.Google Scholar
Lopes, AM, Aston, KI, Thompson, E, et al. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS Genetics. 2013;9:e1003349.Google Scholar
Yatsenko, AN, Georgiadis, AP, Ropke, A, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015;372:20972107.Google Scholar
Oud, MS, Volozonoka, L, Smits, RM, Vissers, L, Ramos, L, Veltman, JA. A systematic review and standardized clinical validity assessment of male infertility genes. Hum Reprod. 2019;34:932941.Google Scholar
Delot, EC, Papp, JC, DSD-TRN Genetics Workgroup, Sandberg, DE, Vilain, E. Genetics of disorders of sex development: the DSD-TRN experience. Endocrinol Metab Clin North Am. 2017;46:519537.Google Scholar
Bianco, SD, Kaiser, UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2009;5:569576.Google Scholar
Eggers, S, Sadedin, S, van den Bergen, JA, et al. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol. 2016;17:243.Google Scholar
Boehm, U, Bouloux, PM, Dattani, MT, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547564.Google Scholar
Jarow, JP, Espeland, MA, Lipshultz, LI Evaluation of the azoospermic patient. J Urol. 1989;142:6265.Google Scholar
Yu, J, Chen, Z, Ni, Y, Li, Z. CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. Hum Reprod. 2012;27:2535.Google Scholar
Patat, O, Pagin, A, Siegfried, A, et al. Truncating mutations in the adhesion G protein-coupled receptor G2 gene ADGRG2 cause an X-linked congenital bilateral absence of vas deferens. Am J Hum Genet. 2016;99:437442.Google Scholar
Yang, B, Wang, J, Zhang, W, et al. Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population. Andrology. 2017;5:954957.Google Scholar
Kasak, L, Laan, M. Monogenic causes of non-obstructive azoospermia: challenges, established knowledge, limitations and perspectives. Hum Genet. 2021;140:135154.Google Scholar
Vockel, M, Riera-Escamilla, A, Tuttelmann, F, Krausz, C. The X chromosome and male infertility. Hum Genet. 2021;140:203215.Google Scholar
Punab, M, Poolamets, O, Paju, P, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:1831.Google Scholar
Krausz, C, Riera-Escamilla, A. Genetics of male infertility. Nat Rev Urol. 2018;15:369384.Google Scholar
Tuttelmann, F, Simoni, M, Kliesch, S, et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLoS ONE. 2011;6:e19426.Google Scholar
Kasak, L, Punab, M, Nagirnaja, L, et al. Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia. Am J Hum Genet. 2018;103:200212.Google Scholar
Krausz, C, Riera-Escamilla, A, Chianese, C, et al. From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia. Genet Med. 2019;21:189194.Google Scholar
Wyrwoll, MJ, Temel, SG, Nagirnaja, L, et al. Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility. Am J Hum Genet. 2020;107:342351.Google Scholar
Dam, AH, Feenstra, I, Westphal, JR. Ramos, L, van Golde, RJ, Kremer, JA. Globozoospermia revisited. Hum Reprod Update. 2007;13:6375.Google Scholar
Harbuz, R, Zouari, R, Pierre, V, et al. A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation. Am J Hum Genet. 2011;88:351361.Google Scholar
Amiri-Yekta, A, Coutton, C, Kherraf, ZE, et al. Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations. Hum Reprod. 2016;31:28722880.Google Scholar
Sha, YW, Wang, X, Xu, X, et al. Novel mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF). Reprod Sci. 2017:1933719117749756.Google Scholar
Wang, WL, Tu, CF, Tan, YQ. Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new? Asian J Androl. 2020;22:236245.Google Scholar
Jung, M, Wells, D, Rusch, J, et al. Unified single-cell analysis of testis gene regulation and pathology in five mouse strains. Elife. 2019;8.Google Scholar
Guo, J, Grow, EJ, Mlcochova, H, et al. The adult human testis transcriptional cell atlas. Cell Res. 2018;28:11411157.Google Scholar
Grabowski, P, Rappsilber, J. A primer on data analytics in functional genomics: how to move from data to insight? Trends Biochem Sci. 2019;44:2132.Google Scholar
Langmead, B, Nellore, A. Cloud computing for genomic data analysis and collaboration. Nat Rev Genet. 2018;19:208219.Google Scholar
Wilfert, AB, Chao, KR, Kaushal, M, et al. Genome-wide significance testing of variation from single case exomes. Nat Genet. 2016;48:14551461.Google Scholar
Komeya, M, Sato, T, Ogawa, T. In vitro spermatogenesis: a century-long research journey, still half way around. Reprod Med Biol. 2018;17:407420.Google Scholar
Ibtisham, F, Wu, J, Xiao, M, et al. Progress and future prospect of in vitro spermatogenesis. Oncotarget. 2017;8:6670966727.Google Scholar
Sato, T, Katagiri, K, Gohbara, A, et al. In vitro production of functional sperm in cultured neonatal mouse testes. Nature. 2011;471:504507.Google Scholar
Coutton, C, Vargas, AS, Amiri-Yekta, A, et al. Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human. Nat Commun. 2018;9:686.Google Scholar
Duquesnoy, P, Escudier, E, Vincensini, L, et al. Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia. Am J Hum Genet. 2009;85:890896.Google Scholar
Kherraf, ZE, Amiri-Yekta, A, Dacheux, D, et al. A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility. Am J Hum Genet. 2018;103:400412.Google Scholar
Yu, J, Wu, H, Wen, Y, et al. Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interference-mediated large-scale functional screening in Drosophila. Hum Mol Genet. 2015;24:14931503.Google Scholar
Ramanagoudr-Bhojappa, R, Carrington, B, Ramaswami, M, et al. Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility. PLoS Genet. 2018;14:e1007821.Google Scholar
Jamsai, D, O’Bryan, MK. Mouse models in male fertility research. Asian J Androl. 2011;13:139151.Google Scholar
Geister, KA, Timms, AE, Beier, DR. Optimizing genomic methods for mapping and identification of candidate variants in ENU mutagenesis screens using inbred mice. G3 (Bethesda). 2018;8:401409.Google Scholar
Kennedy, CL, O’Bryan, MK. N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research. Hum Reprod Update. 2006;12:293301.Google Scholar
De Jonge, C, Barratt, CLR. The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap. Andrology. 2019;7:762768.Google Scholar
Tuttelmann, F, Ruckert, C, Ropke, A. Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20 years of unchanged routine. Med Genet. 2018;30:1220.Google Scholar
Smith, ED, Radtke, K, Rossi, M, et al. Classification of genes: standardized clinical validity assessment of gene-disease associations aids diagnostic exome analysis and reclassifications. Hum Mutat. 2017;38:600608.Google Scholar
Strande, NT, Riggs, ER, Buchanan, AH, et al. Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource. Am J Hum Genet. 2017;100:895906.Google Scholar
Laan, M. Systematic review of the monogenetic causes of male infertility: the first step towards diagnostic gene panels in the andrology clinic. Hum Reprod. 2019;34:783785.Google Scholar

References

Sengupta, P, Borges, E, Dutta, S, Krajewska-Kulak, E. Decline in sperm count in European men during the past 50 years. Hum Exp Toxicol. 2018;37(3):247255.Google Scholar
Levine, H, Jørgensen, N, Martino-Andrade, A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23(6):646659.Google Scholar
Ravitsky, V, Kimmins, S. The forgotten men: rising rates of male infertility urgently require new approaches for its prevention, diagnosis and treatment. Biol Reprod. 2019;101(5):872874.Google Scholar
Jenkins, TG, Aston, KI, Carrell, DT. Sperm epigenetics and aging. Transl Androl Urol. 2018. 7(Suppl 3):S328S335.Google Scholar
Johnson, AA, Akman, K, Calimport, SRG, et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res. 2012;15(5):483494.Google Scholar
Jenkins, TG, Aston, KI, Pflueger, C, Cairns, BR, Carrell, DT. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet. 2014;10(7):e1004458.Google Scholar
Jenkins, TG, Carrell, DT. The sperm epigenome and potential implications for the developing embryo. Reproduction. 2012;143(6):727734.Google Scholar
Jenkins, TG, Aston, KI, Hotaling, JM, Shamsi, MB, Simon, L, Carrell, DT. Teratozoospermia and asthenozoospermia are associated with specific epigenetic signatures. Andrology. 2016;4(5):843849.Google Scholar
Jenkins, TG, Aston, KI, Meyer, TD, et al. Decreased fecundity and sperm DNA methylation patterns. Fertil Steril. 2016;105(1):51–7-e1–3.Google Scholar
Nanassy, L, Carrell, DT. Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination. Asian J Androl. 2011;13(2):342346.Google Scholar
Aoki, VW, Emery, BR, Liu, L, Carrell, DT. Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity. J Androl. 2006;27(6):890898.Google Scholar
Wykes, SM, Krawetz, SA. The structural organization of sperm chromatin. J Biol Chem. 2003;278(32):2947129477.Google Scholar
Hammoud, SS, Nix, DA, Zhang, H, Purwar, J, Carrell, DT, Cairns, BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460(7254):473478.Google Scholar
Aoki, VW, Liu, L, Carrell, DT. A novel mechanism of protamine expression deregulation highlighted by abnormal protamine transcript retention in infertile human males with sperm protamine deficiency. Mol Hum Reprod. 2006;12(1):4150.Google Scholar
Salas-Huetos, A, James, ER, Aston, KI, Carrell, DT, Jenkins, TG, Yeste, M. The role of miRNAs in male human reproduction: a systematic review. Andrology. 2020;8(1):726.Google Scholar
James, ER, Carrell, DT, Aston, KI, Jenkins, TG, Yeste, M, Salas-Huetos, A. The role of the epididymis and the contribution of epididymosomes to mammalian reproduction. Int J Mol Sci. 2020;21(15):5377.Google Scholar
Jodar, M, Sendler, E, Moskovtsev, SI, et al. Absence of sperm RNA elements correlates with idiopathic male infertility. Sci Transl Med. 2015;7(295):295re6.Google Scholar
Aston, KI, Uren, PJ, Jenkins, TG, et al. Aberrant sperm DNA methylation predicts male fertility status and embryo quality. Fertil Steril. 2015;104(6):13881397 e1–5.Google Scholar
Jenkins, TG, Aston, KI, Cairns, B, Smith, A, Carrell, DT. Paternal germ line aging: DNA methylation age prediction from human sperm. BMC Genomics. 2018;19(1):763.Google Scholar

References

Waddington, CH. The epigenotype. 1942. Int J Epidemiol. 2012;41(1):1013.Google Scholar
Waddington, CH. Towards a theoretical biology. Nature. 1968;218:525527.Google Scholar
Santana, V, Salas-Huetos, A, James, ER, Carrell, DT. The effect of endocrine disruptors and environmental and lifestyle factors on the sperm epigenome. In: Aitken, RJ, Mortimer, D, Kovacs, G, eds. Male and Sperm Factors That Maximize IVF Success. Cambridge University Press; 2020:4158.Google Scholar
Jones, RE, Lopez, KH. Human Reproductive Biology. 4th ed. Academic Press; 2004.Google Scholar
Schagdarsurengin, U, Paradowska, A, Steger, K. Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction. Nat Rev Urol. 2012;9(11):609619.Google Scholar
Bowman, GD, Poirier, MG. Post-translational modifications of histones that influence nucleosome dynamics. Chem Rev. 2015;115(6):22742295.Google Scholar
Oliva, R. Protamines and male infertility. Hum Reprod Update. 2006;12(4):417435.Google Scholar
Oliva, R, Castillo, J, Estanyol, J, Ballescà, J. Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility. Asian J Androl. 2015;17(4):601609.Google Scholar
Hammoud, SS, Nix, DA, Zhang, H, Purwar, J, Carrell, DT, Cairns, BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460(7254):473478.Google Scholar
Brykczynska, U, Hisano, M, Erkek, S, et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol. 2010;17(6):679687.Google Scholar
Jin, B, Li, Y, Robertson, KD. DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer. 2011;2(6):607617.Google Scholar
Camprubí, C, Cigliano, RA, Salas-Huetos, A, Garrido, N, Blanco, J. What the human sperm methylome tells us. Epigenomics. 2017;9(10):12991315.Google Scholar
Ha, M, Kim, VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol [Internet]. 2014 [cited 2014 Jul 17];15(8):509524. Available from: www.ncbi.nlm.nih.gov/pubmed/25027649Google Scholar
O’Brien, J, Hayder, H, Zayed, Y, Peng, C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9:112.Google Scholar
Kozomara, A, Griffiths-Jones, S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39:D152D157.Google Scholar
Salas-Huetos, A, Blanco, J, Vidal, F, Mercader, JM, Garrido, N, Anton, E. New insights into the expression profile and function of micro-ribonucleic acid in human spermatozoa. Fertil Steril. 2014;102(1):213222.Google Scholar
Grivna, ST, Beyret, E, Wang, Z, Lin, H. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 2006;20(13):17091714.Google Scholar
He, Z, Kokkinaki, M, Pant, D, Gallicano, GI, Dym, M. Small RNA molecules in the regulation of spermatogenesis. Reproduction. 2009;137(6):901911.Google Scholar
Wang, J, Zhang, P, Lu, Y, et al. PiRBase: a comprehensive database of piRNA sequences. Nucleic Acids Res. 2019;47(D1):D175D180.Google Scholar
Krawetz, SA, Kruger, A, Lalancette, C, et al. A survey of small RNAs in human sperm. Hum Reprod. 2011;26(12):34013412.Google Scholar
Pedroso Ayub, AL, D’Angelo Papaiz, D, da Silva Soares, R, Galvonas, JM. The function of lncRNAs as epigenetic regulators. In: Tutar, L, Aras, S, Tutar, E, eds. Non-Coding RNAs. IntechOpen; 2020:120.Google Scholar
Zhang, X, Gao, F, Fu, J, Zhang, P, Wang, Y, Zeng, X. Systematic identification and characterization of long non-coding RNAs in mouse mature sperm. PLoS ONE. 2017;12(3):e0173402.Google Scholar
Dahariya, S, Paddibhatla, I, Kumar, S, Raghuwanshi, S, Pallepati, A, Gutti, RK. Long non-coding RNA: classification, biogenesis and functions in blood cells. Mol Immunol. 2019;112:8292.Google Scholar
Volders, PJ, Anckaert, J, Verheggen, K, et al. Lncipedia 5: towards a reference set of human long non-coding RNAs. Nucleic Acids Res. 2019;47(D1):D135D139.Google Scholar
Zhang, X, Zhang, P, Song, D, et al. Expression profiles and characteristics of human lncRNA in normal and asthenozoospermia sperm. Biol Reprod. 2019;100(4):982993.Google Scholar
Zhu, L, Ge, J, Li, T, Shen, Y, Guo, J. tRNA-derived fragments and tRNA halves: the new players in cancers. Cancer Lett [Internet]. 2019;452:3137. Available from: doi.org/10.1016/j.canlet.2019.03.012Google Scholar
Kumar, P, Kuscu, C, Dutta, A. Biogenesis and function of transfer RNA related fragments (tRFs). Trends Biochem Sci. 2016;41(8):679689.Google Scholar
Pliatsika, V, Loher, P, Magee, R, et al. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all the Cancer Genome Atlas projects. Nucleic Acids Res. 2018;46(D1):D152D159.Google Scholar
Hua, M, Liu, W, Chen, Y, et al. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discov. 2019;5(1):20.Google Scholar
Trigg, NA, Eamens, AL, Nixon, B. The contribution of epididymosomes to the sperm small RNA profile. Reproduction. 2019;157:R209R223.Google Scholar
Beard, JR, Officer, A, De Carvalho, IA, et al. The world report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387(10033):21452154.Google Scholar
Levine, H, Jørgensen, N, Martino-Andrade, A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23(6):646659.Google Scholar
Vollset, SE, Goren, E, Yuan, C, et al. Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study. Lancet. 2020;396(10258):12851306.Google Scholar
Jenkins, TG, Aston, KI, Pflueger, C, Cairns, BR, Carrell, DT. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet. 2014;10(7):e1004458.Google Scholar
Jenkins, TG, James, ER, Aston, KI, et al. Age‑associated sperm DNA methylation patterns do not directly persist trans‑generationally. Epigenetics Chromatin. 2019;12:74.Google Scholar
Salas-Huetos, A, Blanco, J, Vidal, F, et al. Spermatozoa from patients with seminal alterations exhibit a differential micro-ribonucleic acid profile. Fertil Steril. 2015;104(3):591601.Google Scholar
Bhaskaran, K, Douglas, I, Forbes, H, Dos-Santos-Silva, I, Leon, DA, Smeeth, L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet. 2014;384(9945):755765.Google Scholar
Salas-Huetos, A, Maghsoumi-Norouzabad, L, James, ER, et al. Male adiposity, sperm parameters and reproductive hormones: an updated systematic review and collaborative meta-analysis. Obes Rev. 2021;22(1):e13082.Google Scholar
Craig, JR, Jenkins, TG, Carrell, DT, Hotaling, JM. Obesity, male infertility, and the sperm epigenome. Fertil Steril. 2017;107(4):848859.Google Scholar
Soubry, A, Guo, L, Huang, Z, et al. Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics. 2016;8(1):111.Google Scholar
Fullston, T, Ohlsson Teague, EMC, Palmer, NO, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J. 2013;27(10):42264243.Google Scholar
Merzenich, H, Zeeb, H, Blettner, M. Decreasing sperm quality: a global problem? BMC Public Health. 2010;10(24):15.Google Scholar
Salas-Huetos, A, Bulló, M, Salas-Salvadó, J. Dietary patterns, foods and nutrients in male fertility parameters and fecundability: a systematic review of observational studies. Hum Reprod Update. 2017;23(4):371389.Google Scholar
Gaskins, AJ, Chavarro, JE. Diet and fertility: a review. Am J Obstet Gynecol. 2017;218(4):379389.Google Scholar
Salas-Huetos, A, Rosique-Esteban, N, Becerra-Tomás, N, Vizmanos, B, Bulló, M, Salas-Salvadó, J. The effect of nutrients and dietary supplements on sperm quality parameters: a systematic review and meta-analysis of randomized clinical trials. Adv Nutr An Int Rev J. 2018;9(6):833848.Google Scholar
Salas-Huetos, A, Babio, N, Carrell, DT, Bulló, M, Salas-Salvadó, J. Adherence to the Mediterranean diet is positively associated with sperm motility: a cross-sectional analysis. Sci Rep. 2019;9(1):3389.Google Scholar
Xue, J, Gharaibeh, RZ, Pietryk, EW, et al. Impact of vitamin D depletion during development on mouse sperm DNA methylation. Epigenetics. 2018;13(9):959974.Google Scholar
Lambrot, R, Xu, C, Saint-Phar, S, et al. Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat Commun. 2013;4:2889.Google Scholar
Chan, D, McGraw, S, Klein, K, et al. Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation. Hum Reprod. 2017;32(2):272283.Google Scholar
Aarabi, M, Christensen, KE, Chan, D, et al. Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation. Hum Mol Genet. 2018;27(7):11231135.Google Scholar
Aarabi, M, San Gabrie, MC, Chan, D, et al. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet. 2015;24(22):63016313.Google Scholar
Watkins, AJ, Dias, I, Tsuro, H, et al. Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proc Natl Acad Sci U S A. 2018;115(40):1006410069.Google Scholar
Claycombe-Larson, KG, Bundy, AN, Roemmich, JN. Paternal high-fat diet and exercise regulate sperm miRNA and histone methylation to modify placental inflammation, nutrient transporter mRNA expression and fetal weight in a sex-dependent manner. J Nutr Biochem. 2020;81:108373.Google Scholar
Nätt, D, Kugelberg, U, Casas, E, et al. Human sperm displays rapid responses to diet. PLoS Biol. 2019;17(12):e3000559.Google Scholar
Salas-Huetos, A, Moraleda, R, Giardina, S, et al. Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial. Am J Clin Nutr. 2018;108(5):953962.Google Scholar
Sharma, R, Harlev, A, Agarwal, A, Esteves, SC. Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010 World Health Organization laboratory methods for the examination of human semen. Eur Urol. 2016;70(4):635645.Google Scholar
Marczylo, EL, Amoako, AA, Konje, JC, Gant, TW, Marczylo, TH. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics. 2012;7(5):432439.Google Scholar
Hamad, MF, Dayyih, WAA, Laqqan, M, AlKhaled, Y, Montenarh, M, Hammadeh, ME. The status of global DNA methylation in the spermatozoa of smokers and non-smokers. Reprod Biomed Online. 2018;37(5):581589.Google Scholar
Alkhaled, Y, Laqqan, M, Tierling, S, Lo Porto, C, Amor, H, Hammadeh, ME. Impact of cigarette-smoking on sperm DNA methylation and its effect on sperm parameters. Andrologia. 2018;50(4):e12950.Google Scholar
Jenkins, TG, James, ER, Alonso, DF, et al. Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology. 2017;5(6):10891099.Google Scholar
Murphy, PJ, Guo, J, Jenkins, TG, et al. NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure. PLoS Genet. 2020;16(6):e1008756.Google Scholar

References

Khandwala, YS, Baker, VL, Shaw, GM, Stevenson, DK, Lu, Y, Eisenberg, ML. Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population based cohort study. BMJ. 2018;363:18. doi:10.1136/bmj.k4372Google Scholar
Sauer, MV. Reproduction at an advanced maternal age and maternal health. Fertil Steril. 2015;103(5):11361143. doi:10.1016/j.fertnstert.2015.03.004Google Scholar
Jenkins, TG, Aston, KI, Pflueger, C, Cairns, BR, Carrell, DT. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet. 2014;10(7):113. doi:10.1371/journal.pgen.1004458Google Scholar
Jenkins, TG, Aston, KI, Cairns, BR, Carrell, DT. Paternal aging and associated intraindividual alterations of global sperm 5-methylcytosine and 5-hydroxymethylcytosine levels. Fertil Steril. 2013;100(4):945951.e2. doi:10.1016/j.fertnstert.2013.05.039Google Scholar
Johnson, SL, Dunleavy, J, Gemmell, NJ, Nakagawa, S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev. 2015;19:2233. doi:10.1016/j.arr.2014.10.007Google Scholar
Santi, D, Spaggiari, G, Simoni, M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses. Reprod Biomed Online. 2018;37(3):315326. doi:10.1016/j.rbmo.2018.06.023Google Scholar
Tan, J, Taskin, O, Albert, A, Bedaiwy, MA. Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis. Reprod Biomed Online. 2019;38(6):951960. doi:10.1016/j.rbmo.2018.12.029Google Scholar
Cocuzza, M, Athayde, KS, Agarwal, A, et al. Age-related increase of reactive oxygen species in neat semen in healthy fertile men. Urology. 2008;71(3):490494. doi:10.1016/j.urology.2007.11.041Google Scholar
Maher, GJ, Goriely, A, Wilkie, AOM. Cellular evidence for selfish spermatogonial selection in aged human testes. Andrology. 2013;2:304314. doi:10.1111/j.2047-2927.2013.00175.xGoogle Scholar
Selvin, E, Burnett, AL, Platz, EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007;120:151157. doi:10.1016/j.amjmed.2006.06.010Google Scholar
Agarwal, A, Gupta, S, Du, Plessis S, et al. Abstinence time and its impact on basic and advanced semen parameters. Urology. 2016;94:102110. doi:10.1016/j.urology.2016.03.059Google Scholar
Paduch, D, Polzer, P, Morgentaler, A, et al. Clinical and demographic correlates of ejaculatory dysfunctions other than premature ejaculation: a prospective, observational study. J Sex Med. 2015;12:22762286. doi:10.1111/jsm.13027Google Scholar
Kasman, AM, Bhambhvani, HP, Eisenberg, ML. Ejaculatory dysfunction in patients presenting to a men’s health clinic: a retrospective cohort study. Sex Med. 2020;8(3):454460. doi:10.1016/j.esxm.2020.05.002Google Scholar
Avellino, G, Theva, D, Oates, RD. Common urologic diseases in older men and their treatment: how they impact fertility. Fertil Steril. 2017;107(2):305311. doi:10.1016/j.fertnstert.2016.12.008Google Scholar
Mahabadi, V, Amory, JK, Swerdloff, RS, et al. Combined transdermal testosterone gel and the gonadotropins in men. J Clin Endocrinol Metab. 2009;94(7):23132320. doi:10.1210/jc.2008-2604Google Scholar
Kohn, TP, Louis, MR, Pickett, SM, et al. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril. 2017;107(2):351357.e1. doi:10.1016/j.fertnstert.2016.10.004Google Scholar
Wang, C, Swerdloff, RS. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil Steril. 2014;102(6):15021507. doi:10.1016/j.fertnstert.2014.10.021Google Scholar
Kidd, SA, Eskenazi, B, Wyrobek, AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237248. doi:10.1016/s0015-0282(00)01679-4Google Scholar
Li, WN, Jia, MM, Peng, YQ, Ding, R, Fan, LQ, Liu, G. Semen quality pattern and age threshold: a retrospective cross-sectional study of 71,623 infertile men in China, between 2011 and 2017. Reprod Biol Endocrinol. 2019;17(107):18. doi:10.1186/s12958-019-0551-2Google Scholar
Priskorn, L, Jensen, TK, Lindahl-Jacobsen, R, Skakkebæk, NE, Bostofte, E, Eisenberg, ML. Parental age at delivery and a man’s semen quality. Hum Reprod. 2014;29(5):10971102. doi:10.1093/humrep/deu039Google Scholar
Verón, GL, Tissera, AD, Bello, R, Beltramone, F, Estofan, G, Molina, RI, Vazquez-Levin, MH. Impact of age, clinical conditions, and lifestyle on routine semen parameters and sperm kinematics. Fertil Steril. 2018;110(1):6875e3. doi:10.1016/j.fertnstert.2018.03.016.Google Scholar
Seymour, F, Duffy, C, Koerner, A. A case of authenticated fertility in a man, aged 94. JAMA. 1935;105(18):14231424.Google Scholar
Johnson, S, Dunleavy, J, Gemmell, N, Nakagawa, S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev. 2015;19:2233. doi:10.1016/j.arr.2014.10.007Google Scholar
Conti, SL, Eisenberg, ML. Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer. Asian J Androl. 2016;18(3):420424. doi:10.4103/1008-682X.175097Google Scholar
Hamilton, B, Hoyert, D, Martin, J, Strombino, D, Guyer, B. Annual summary of vital statistics: 2010–2011. Pediatrics. 2013;131(3):548558. doi:10.1542/peds.2012-3769Google Scholar
Khandwala, Y, Zhang, C, Lu, Y, Eisenberg, M. The age of fathers in the USA is rising: an analysis of 168,867,480 births from 1972 to 2015. Hum Reprod. 2017;32(10):21102116. doi:10.1093/humrep/dex267Google Scholar
Mazur, DJ, Lipshultz, LI. Infertility in the aging male. Curr Urol Rep. 2018;19(7):54. doi:10.1007/s11934-018-0802-3Google Scholar
Oldereid, NB, Wennerholm, U, Pinborg, A, et al. The effect of paternal factors on perinatal and paediatric outcomes: a systematic review and meta-analysis. Hum Reprod Update. 2018;24(3):320389. doi:10.1093/humupd/dmy005Google Scholar
Ford, W, North, K, Taylor, H, Farrow, A, Hull, M, Golding, J. Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood). Hum Reprod. 2000;15(8):17031708. doi:10.1093/humrep/15.8.1703Google Scholar
Hassan, M, Killick, S. Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril. 2003;79(Suppl. 3):15201527. doi:10.1016/s0015-0282(03)00366-2Google Scholar
de la Rochebrochard, E, Thonneau, P. Paternal age >or=40 years: an important risk factor for infertility. Am J Obs Gynecol. 2003;189(4):901905. doi:10.1067/s0002-9378(03)00753-1Google Scholar
Dain, L, Auslander, R, Dirnfeld, M. The effect of paternal age on assisted reproduction outcome. Fertil Steril. 2011;95(1):18. doi:10.1016/j.fertnstert.2010.08.029Google Scholar
Whitcomb, B, Levens, E, Turzanski-Fortner, R, et al. Contribution of male age to outcomes in assisted reproductive technologies. Fertil Steril. 2011;95(1):147151. doi:10.1016/j.fertnstert.2010.06.039Google Scholar
Mathieu, C, Ecochard, R, Bied, V, Lornage, J, Czyba, J. Cumulative conception rate following intrauterine artificial insemination with husband’s spermatozoa: influence of husband’s age. Hum Reprod. 1995;10(5):10901097. doi:10.1093/oxfordjournals.humrep.a136100Google Scholar
McPherson, N, Zander-Fox, D, Vincent, A, Lane, M. Combined advanced parental age has an additive negative effect on live birth rates – data from 4057 first IVF/ICSI cycles. J Assist Reprod Genet. 2018;35(2):279287. doi:10.1007/s10815-017-1054-8Google Scholar
Wu, Y, Kang, X, Zheng, H, Liu, H, Liu, J. Effect of paternal age on reproductive outcomes of in vitro fertilization. PLoS ONE. 2015;10(9):19. doi:10.1371/journal.pone.0135734Google Scholar
Kaarouch, I, Bouamoud, N, Madkour, A, et al. Paternal age: negative impact on sperm genome decays and IVF outcomes after 40 years. Mol Reprod Dev. 2018;85(3):271280. doi:10.1002/mrd.22963Google Scholar
Hajj, N, Zechner, U, Schneider, E, et al. Methylation status of imprinted genes and repetitive elements in sperm DNA from infertile males. Sex Dev. 2011;5:6069. doi:10.1159/000323806Google Scholar
Montjean, D, Ravel, C, Benkhalifa, M, et al. Methylation changes in mature sperm deoxyribonucleic acid from oligozoospermic men: assessment of genetic variants and assisted reproductive technology outcome. Fertil Steril. 2013;100(5):12411247.Google Scholar
de la Rochebrochard, E, de Mouzon, J, Thepot, F, Thonneau, P, French National IVF Registry (FIVNAT) Association. Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril. 2006;85(5):14201424. doi:10.1016/j.fertnstert.2005.11.040Google Scholar
Robertshaw, I, Khoury, J, Abdallah, ME, Warikoo, P, Hofmann, GE. The effect of paternal age on outcome in assisted reproductive technology using the ovum donation model. Reprod Sci. 2014;21(5):590593. doi:10.1177/1933719113506497Google Scholar
Begeria, R, Garcia, D, Obradors, A, Poisot, F, Vassena, R, Vernaeve, V. Paternal age and assisted reproductive outcomes in ICSI donor oocytes: is there an effect of older fathers? Hum Reprod. 2014;29(10):21142122. doi:10.1093/humrep/deu189Google Scholar
Frattarelli, JL, Miller, KA, Miller, BT, et al. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril. 2008;90(1):97103. doi:10.1016/j.fertnstert.2007.06.009Google Scholar
Sagi-dain, L, Sagi, S, Dirnfeld, M. Effect of paternal age on reproductive outcomes in oocyte donation model: a systematic review. Fertil Steril. 2015;104(4):857865.e1. doi:10.1016/j.fertnstert.2015.06.036Google Scholar
Bergh, C, Pinborg, A, Wennerholm, U. Parental age and child outcomes. Fertil Steril. 2019;111(6):10361046. doi:10.1016/j.fertnstert.2019.04.026Google Scholar
Mayo, JA, Lu, Y, Stevenson, DK, Shaw, GM, Eisenberg, ML. Parental age and stillbirth: a population-based cohort of nearly 10 million California deliveries from 1991 to 2011. Ann Epidemiol. 2019;31:3237.e2. doi:10.1016/j.annepidem.2018.12.001Google Scholar
Taylor, JL, Debost, JPG, Morton, SU, et al. Paternal-age-related de novo mutations and risk for five disorders. Nat Commun. 2019;10(3043):19. doi:10.1038/s41467-019-11039-6Google Scholar
Contreras, ZA, Hansen, J, Ritz, B, Olsen, J, Yu, F, Heck, JE. Parental age and childhood cancer risk: a Danish population-based registry study. Cancer Epidemiol. 2017;49:202215. doi:10.1016/j.canep.2017.06.010Google Scholar
Wang, R, Metayer, C, Morimoto, L, et al. Parental age and risk of pediatric cancer in the offspring: a population-based record-linkage study in California. Am J Epidemiol. 2017;186(7):843856. doi:10.1093/aje/kwx160Google Scholar
Kasman, AM, Giudice, D, Eisenberg, ML. New insights to guide patient care: the bidirectional relationship between male infertility and male health. Fertil Steril. 2020;113(3):469477. doi:10.1016/j.fertnstert.2020.01.002Google Scholar
Del Giudice, F, Kasman, A, De Berardinis, E, Busseto, G, Belladelli, F, Eisenberg, ML. Association between male infertility and male specific malignancies: systematic review and metanalysis of the population-based retrospective cohort studies. Fertil Steril. 2020;114(5):984996. doi: 10.1016/j.fertnstert.2020.04.042Google Scholar
Del Giudice, F, Kasman, A, Ferro, M, et al. Clinical correlation among male infertility and overall male health: a systematic review of the literature. Investig Clin Urol. 2020;61(4):355371. doi:10.4111/icu.2020.61.4.355Google Scholar

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