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Chapter 2 - Cellular Architecture and Function of the Testis

from Section 1 - Scientific Foundations of Male Infertility

Published online by Cambridge University Press:  08 July 2023

By
Siwen Wu ,
Lingling Wang  and
C. Yan Cheng
Edited by
Larry I. Lipshultz ,
Stuart S. Howards ,
Craig S. Niederberger  and
Dolores J. Lamb
Larry I. Lipshultz
Affiliation:
Baylor College of Medicine, Texas
Stuart S. Howards
Affiliation:
University of Virginia
Craig S. Niederberger
Affiliation:
University of Illinois, Chicago
Dolores J. Lamb
Affiliation:
Weill Cornell Medical College, New York
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Summary

The cellular architecture of the mammalian testis that supports testis function, which, in turn, maintains spermatogenesis throughout adulthood to produce millions of sperm on a daily basis from rodents to humans, has been eminently reviewed by investigators in recent years, based on morphological, biochemical, and molecular studies [1–10]. As such, in order to avoid a repetitive account on this topic, compared with earlier reviews, we attempt to provide insightful information on this topic based on recent studies which have not been evaluated in details, as noted in the following sections. Thus, this avoids redundancy because readers can refer to the earlier reviews pertinent to the cellular architecture of the testis that supports spermatogenesis as reviewed in [1–10]. It is conceivable that some necessary discussion still overlap with earlier reviews or earlier editions of this reference work. This is done such that readers can follow through the discussion here without the necessity of going through other contents to grasp related facts and concepts. Nonetheless, we will refer to other reviews for additional discussion on specific topics in this chapter when a detailed and redundant description is not warranted.

Type
Chapter
Information
Infertility in the Male , pp. 17 - 38
Publisher: Cambridge University Press
Print publication year: 2023

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References

Hermo, L, Oliveira, RL, Smith, CE, Au, CE, Bergeron, JJM. Golgi apparatus regulation of differentiation: a case study for germ cells of the rat testis. In: Cheng, CY, ed. Spermatogenesis: Biology and Clinical Implications. London: CRC Press, 2019; pp. 1–39.Google Scholar
Hermo, L, Pelletier, RM, Cyr, DG, Smith, CE. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germ cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation. Microsc Res Tech 2010;73:409–94.Google Scholar
Hermo, L, Pelletier, RM, Cyr, DG, Smith, CE. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes. Microsc Res Tech 2010;73:241–78.Google Scholar
Hermo, L, Pelletier, RM, Cyr, DG, Smith, CE. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 2: changes in spermatid organelles associated with development of spermatozoa. Microsc Res Tech 2010;73:279–319.Google Scholar
de Kretser, DM, Kerr, JB. The cytology of the testis. In: Knobil, E, Neill, JB, Ewing, LL, Greenwald, GS, Markert, CL, Pfaff, DW, eds. The Physiology of Reproduction, Vol. 1. New York, NY: Raven Press, 1988; pp. 837–932.Google Scholar
O’Donnell, L. Mechanisms of spermiogenesis and spermiation and how they are disturbed. Spermatogenesis 2014;4:e979623.Google Scholar
O’Donnell, L, O’Bryan, MK. Microtubules and spermatogenesis. Semin Cell Dev Biol 2014;30:45–54.Google Scholar
Hess, RA, de Franca, LR. Spermatogenesis and cycle of the seminiferous epithelium. Adv Exp Med Biol 2008;636:1–15.Google ScholarPubMed
Griswold, MD. 50 years of spermatogenesis: Sertoli cells and their interactions with germ cells. Biol Reprod 2018;99:87–100.Google Scholar
Griswold, MD. Spermatogenesis: the commitment to meiosis. Physiol Rev 2016;96:1–17.CrossRefGoogle ScholarPubMed
McCarrey, J. Development of the germ cell. In: Desjardins, C, Ewing, L, eds. Cell and Molecular Biology of the Testis. New York, NY: Oxford University Press, 1993; pp. 58–89.Google Scholar
Amann, RP. The cycle of the seminiferous epithelium in humans: a need to revisit? J Androl 2008;29:469–87.CrossRefGoogle ScholarPubMed
Muciaccia, B, Boitani, C, Berloco, BP, et al. Novel stage classification of human spermatogenesis based on acrosome development. Biol Reprod 2013;89:60.CrossRefGoogle ScholarPubMed
Vogl, AW, Vaid, KS, Guttman, JA. The Sertoli cell cytoskeleton. Adv Exp Med Biol 2008;636:186–211.CrossRefGoogle ScholarPubMed
Russell, LD, Peterson, RN. Sertoli cell junctions: morphological and functional correlates. Int Rev Cytol 1985;94:177–211.CrossRefGoogle ScholarPubMed
Wong, EWP, Mruk, DD, Cheng, CY. Biology and regulation of ectoplasmic specialization, an atypical adherens junction type, in the testis. Biochem Biophys Acta 2008;1778:692–708.Google Scholar
Mruk, DD, Cheng, CY. Cell–cell interactions at the ectoplasmic specialization in the testis. Trends Endocrinol Metab 2004;15:439–47.Google Scholar
Mruk, DD, Cheng, CY. Sertoli–Sertoli and Sertoli–germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 2004;25:747–806.Google Scholar
Wong, EWP, Cheng, CY. Polarity proteins and cell–cell interactions in the testis. Int Rev Cell Mol Biol 2009;278:309–53.CrossRefGoogle ScholarPubMed
Assemat, E, Bazellieres, E, Pallesi-Pocachard, E, Le Bivic, A, Massey-Harroche, D. Polarity complex proteins. Biochim Biophys Acta 2008;1778:614–30.Google Scholar
Iden, S, Collard, JG. Crosstalk between small GTPases and polarity proteins in cell polarization. Nat Rev Mol Cell Biol 2008;9:846–59.Google Scholar
Wong, EWP, Mruk, DD, Lee, WM, Cheng, CY. Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood–testis barrier restructuring during spermatogenesis. Proc Natl Acad Sci U S A 2008;105:9657–62.Google Scholar
Wong, EWP, Sun, S, Li, MWM, Lee, WM, Cheng, CY. 14-3-3 protein regulates cell adhesion in the seminiferous epithelium of rat testes. Endocrinology 2009;150:4713–23.CrossRefGoogle ScholarPubMed
Gao, Y, Lui, WY, Lee, WM, Cheng, CY. Polarity protein Crumbs homolog-3 (CRB3) regulates ectoplasmic specialization dynamics through its action on F-actin organization in Sertoli cells. Sci Rep 2016;6:28589.Google Scholar
Su, WH, Wong, EWP, Mruk, DD, Cheng, CY. The Scribble/Lgl/Dlg polarity protein complex is a regulator of blood–testis barrier dynamics and spermatid polarity during spermatogenesis. Endocrinology 2012;153:6041–53.Google Scholar
Chen, H, Xiao, X, Lui, WY, Lee, WM, Cheng, CY. Vangl2 regulates spermatid planar cell polarity through microtubule (MT)-based cytoskeleton in the rat testis. Cell Death Dis 2018;9:340.Google Scholar
Chen, H, Mruk, DD, Lee, WM, Cheng, CY. Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane-derived noncollagenous 1 domain peptide. FASEB J 2017;31:3587–607.Google ScholarPubMed
Montcouquiol, M, Kelley, MW. Development and patterning of the cochlea: from convergent extension to planar polarity. Cold Spring Harb Perspect Med 2020;10:a033266.CrossRefGoogle ScholarPubMed
Tarchini, B, Lu, X. New insights into regulation and function of planar polarity in the inner ear. Neurosci Lett 2019;709:134373.Google Scholar
Axelrod, JD. Planar cell polarity signaling in the development of left–right asymmetry. Curr Opin Cell Biol 2020;62:61–9.Google Scholar
Sutherland, A, Keller, R, Lesko, A. Convergent extension in mammalian morphogenesis. Semin Cell Dev Biol 2020;100:199–211.Google Scholar
Fisher, KH, Strutt, D. A theoretical framework for planar polarity establishment through interpretation of graded cues by molecular bridges. Development 2019;146:dev168955.Google Scholar
Chen, H, Mruk, DD, Lee, WM, Cheng, CY. Planar cell polarity (PCP) protein Vangl2 regulates ectoplasmic specialization dynamics via its effects on actin microfilaments in the testes of male rats. Endocrinology 2016;157:2140–59.CrossRefGoogle ScholarPubMed
Li, L, Mao, B, Yan, M, et al. Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organization. Cell Death Dis 2019;10:194.Google Scholar
Parvinen, M. Regulation of the seminiferous epithelium. Endocr Rev 1982;3:404–17.Google Scholar
Clermont, Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 1972;52:198–235.Google Scholar
Clermont, Y. The cycle of the seminiferous epithelium in man. Am J Anat 1963;112:35–51.Google Scholar
Leblond, CP, Clermont, Y. Spermiogenesis of rat, mouse, hamster, and guinea pig as revealed by the periodic acid-fuchin sulfurous acid technique. Am J Anat 1952;90:167–210.Google Scholar
Hess, RA. Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: light microscopic observations of perfusion-fixed and plastic-embedded testes. Biol Reprod 1990;43:525–42.Google Scholar
Xiao, X, Mruk, DD, Wong, CKC, Cheng, CY. Germ cell transport across the seminiferous epithelium during spermatogenesis. Physiology 2014;29:286–98.Google Scholar
Wong, V, Russell, LD. Three-dimensional reconstruction of a rat stage V Sertoli cell: I. Methods, basic configuration, and dimensions. Am J Anat 1983;167:143–61.Google Scholar
Russell, LD, Tallon-Doran, M, Weber, JE, Wong, V, Peterson, RN. Three-dimensional reconstruction of a rat stage V Sertoli cell: III. A study of specific cellular relationships. Am J Anat 1983;167:181–92.Google Scholar
Weber, JE, Russell, LD, Wong, V, Peterson, RN. Three dimensional reconstruction of a rat stage V Sertoli cell: II. Morphometry of Sertoli–Sertoli and Sertoli–germ cell relationships. Am J Anat 1983;167:163–79.Google Scholar
Vaidžiulytė, K, Coppey, M, Schauer, K. Intracellular organization in cell polarity – placing organelles into the polarity loop. J Cell Sci 2019;132:jcs230995.Google Scholar
Riga, A, Castiglioni, VG, Boxem, M. New insights into apical-basal polarization in epithelia. Curr Opin Cell Biol 2020;62:1–8.Google Scholar
Bazellieres, E, Aksenova, V, Barthelemy-Requin, M, Massey-Harroche, D, Le Bivic, A. Role of the Crumbs proteins in ciliogenesis, cell migration and actin organization. Semin Cell Dev Biol 2018;81:13–20.Google Scholar
Peglion, F, Goehring, NW. Switching states: dynamic remodelling of polarity complexes as a toolkit for cell polarization. Curr Opin Cell Biol 2019;60:121–30.Google Scholar
Montcouguiol, M, Kelley, MW. Development and patterning of the cochlea: From convergent extension to planar polarity. Cold Spring Harb Perspect Med 2020;10:a033266.Google Scholar
Bonello, TT, Peifer, M. Scribble: a master scaffold in polarity, adhesion, synaptogenesis, and proliferation. J Cell Biol 2019;218:742–56.Google Scholar
Chen, H, Mruk, DD, Lui, WY, Wong, CKC, Lee, WM, Cheng, CY. Cell polarity and planar cell polarity (PCP) in spermatogenesis. Semin Cell Dev Biol 2018;81:71–7.Google Scholar
Aw, WY, Heck, BW, Joyce, B, Devenport, D. Transient tissue-scale deformation coordinates alignment of planar cell polarity junctions in the mammalian skin. Curr Biol 2016;26:2090–100.Google Scholar
Satir, P. Chirality of the cytoskeleton in the origins of cellular asymmetry. Philos Trans R Soc Lond B Biol Sci 2016;371:20150408.CrossRefGoogle ScholarPubMed
Taylor, J, Abramova, N, Charlton, J, Adler, PN. Van Gogh: a new Drosophila tissue polarity gene. Genetics 1998;150:199–210.Google Scholar
Aw, WY, Devenport, D. Planar cell polarity: global inputs establishing cellular asymmetry. Curr Opin Cell Biol 2017;44:110–16.Google Scholar
Goodrich, LV, Strutt, D. Principles of planar polarity in animal development. Development 2011;138:1877–92.Google Scholar
Xie, Y, Miao, H, Blankenship, JT. Membrane trafficking in morphogenesis and planar polarity. Traffic 2018. doi: 10.1111/tra.12580.Google Scholar
Li, L, Chen, H, Lian, QQ, Ge, RS, Cheng, CY. Does planar cell polarity matter during spermatogenesis? In: Cheng, CY, ed. Spermatogenesis: Biology and Clinical Implications. London: CRC Press/Taylor & Francis Group, 2018; pp. 211–19.Google Scholar
Park, TJ, Haigo, SL, Wallingford, JB. Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Nat Genet 2006;38:303–11.Google Scholar
Sokol, SY. Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development. Semin Cell Dev Biol 2015;42:78–85.Google Scholar
Goffinet, AM, Tissir, F. Seven pass cadherins CELSR1–3. Semin Cell Dev Biol 2017;69:102–10.Google Scholar
May-Simera, H, Kelley, MW. Planar cell polarity in the inner ear. Curr Top Dev Biol 2012;101:111–40.Google Scholar
Humphries, AC, Mlodzik, M. From instruction to output: Wnt/PCP signaling in development and cancer. Curr Opin Cell Biol 2018;51:110–16.Google Scholar
Yang, Y, Mlodzik, M. Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt). Annu Rev Cell Dev Biol 2015;31:623–46.Google Scholar
Li, L, Chen, H, Lian, Q, Ge, RS, Cheng, CY. Does planar cell polarity matter during spermatogenesis? In: Cheng, CY, ed. Spermatogenesis: Biology and Clinical Implications. London: CRC Press/Taylor & Francis Group, 2018; pp. 211–19.Google Scholar
White, JJ, Mazzeu, JF, Hoischen, A, et al. DVL3 alleles resulting in a −1 frameshift of the last exon mediate autosomal-dominant Robinow syndrome. Am J Hum Genet 2016;98:553–61.Google Scholar
White, JJ, Mazzeu, JF, Coban-Akdemir, Z, et al. WNT signaling perturbations underlie the genetic heterogeneity of Robinow syndrome. Am J Hum Genet 2018;102:27–43.Google Scholar
Horbelt, CV. Robinow syndrome, Cockayne syndrome, and Pfeiffer syndrome: an overview of physical, neurological, and oral characteristics. Gen Dent 2010;58:14–17.Google Scholar
Lei, YP, Zhang, T, Li, H, Wu, BL, Jin, L, Wang, HY. VANGL2 mutations in human cranial neural-tube defects. N Engl J Med 2010;362:2232–5.Google Scholar
Hermo, L, Pelletier, RM, Cyr, DG, Smith, CE. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage-gated channels, methylation/acetylation, and transcription factors. Microsc Res Tech 2010;73:364–408.Google Scholar
Dym, M. Basement membrane regulation of Sertoli cells. Endocr Rev 1994;15:102–15.Google Scholar
Siu, MKY, Cheng, CY. Dynamic cross-talk between cells and the extracellular matrix in the testis. Bioessays 2004;26:978–92.Google Scholar
Koch, M, Olson, PF, Albus, A, et al. Characterization and expression of the laminin γ3 chain: a novel, non-basement membrane-associated, laminin chain. J Cell Biol 1999;145:605–18.Google Scholar
Yan, HHN, Cheng, CY. Laminin α3 forms a complex with β3 and γ3 chains that serves as the ligand for α6β1-integrin at the apical ectoplasmic specialization in adult rat testes. J Biol Chem 2006;281:17286–303.Google Scholar
Siu, MKY, Cheng, CY. Interactions of proteases, protease inhibitors, and the β1 integrin/laminin γ3 protein complex in the regulation of ectoplasmic specialization dynamics in the rat testis. Biol Reprod 2004;70:945–64.Google Scholar
Palombi, F, Salanova, M, Tarone, G, Farini, D, Stefanini, M. Distribution of β1 integrin subunit in rat seminiferous epithelium. Biol Reprod 1992;47:1173–82.Google Scholar
Salanova, M, Stefanini, M, De Curtis, I, Palombi, F. Integrin receptor α6β1 is localized at specific sites of cell-to-cell contact in rat seminiferous epithelium. Biol Reprod 1995;52:79–87.Google Scholar
Salanova, M, Ricci, G, Boitani, C, Stefanini, M, De Grossi, S, Palombi, F. Junctional contacts between Sertoli cells in normal and aspermatogenic rat seminiferous epithelium contain α6β1 integrins, and their formation is controlled by follicle-stimulating hormone. Biol Reprod 1998;58:371–8.Google Scholar
Su, L, Mruk, DD, Lie, PPY, Silvestrini, B, Cheng, CY. A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats. Nat Commun 2012;3:1185.Google Scholar
Gao, Y, Mruk, DD, Lui, WY, Lee, WM, Cheng, CY. F5-peptide induces aspermatogenesis by disrupting organization of actin- and microtubule-based cytoskeletons in the testis. Oncotarget 2016;7:64203–20.Google Scholar
Lie, PPY, Mruk, DD, Mok, KW, Su, L, Lee, WM, Cheng, CY. Focal adhesion kinase-Tyr407 and -Tyr397 exhibit antagonistic effects on blood–testis barrier dynamics in the rat. Proc Natl Acad Sci U S A 2012;109:12562–7.Google Scholar
Chen, H, Gao, Y, Mruk, DD, et al. Rescue of PFOS-induced human Sertoli cell injury by overexpressing a p-FAK-Y407E phosphomimetic mutant. Sci Rep 2017;7:15810.Google Scholar
Siu, MKY, Cheng, CY. Extracellular matrix: recent advances on its role in junction dynamics in the seminiferous epithelium during spermatogenesis. Biol Reprod 2004;71:375–91.Google Scholar
Timpl, R, Brown, J. Supramolecular assembly of basement membranes. Bioessays 1996;18:123–32.Google Scholar
Timpl, R, Wiedemann, H, van Delden, V, Furthmayr, H, Kuhn, K. A network model for the organization of type IV collagen molecules in basement membranes. Eur J Biochem 1989;120:203–11.Google Scholar
Hudson, BG, Reeders, ST, Tryggvason, K. Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem 1993;268:26033–6.Google Scholar
Prockop, DJ, Kivirikko, KI. Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 1995;64:403–34.Google Scholar
Gatseva, A, Sin, YY, Brezzo, G, Van Agtmael, T. Basement membrane collagens and disease mechanisms. Essays Biochem 2019;63:297–312.Google ScholarPubMed
Oh, SP, Warman, ML, Seldin, MF, et al. Cloning of cDNA and genomic DNA encoding human type XVIII collagen and localization of the α1 (XVIII) collagen gene to mouse chromosome 10 and human chromosome 21. Genomics 1994;19:494–9.Google Scholar
Davis, CM, Papadopoulos, V, Sommers, CL, Kleinman, HK, Dym, M. Differential expression of extracellular matrix components in rat Sertoli cells. Biol Reprod 1990;43:860–9.Google Scholar
Enders, GC, Kahsai, TZ, Lian, G, Funabiki, K, Killen, PD, Hudson, BG. Developmental changes in seminiferous tubule extracellular matrix components of the mouse testis: α3 (IV) collagen chain expressed at the initiation of spermatogenesis. Biol Reprod 1995;53:1489–99.Google Scholar
Fröjdman, K, Pelliniemi, LJ, Virtanen, I. Differential distribution of type IV collagen chains in the developing rat testis and ovary. Differentiation 1998;63:125–30.Google Scholar
Miner, JH, Sanes, RJ. Molecular and functional defects in kidneys of mice lacking collagen α3(IV): implications for Alport syndrome. J Cell Biol 1996;135:1402–13.Google Scholar
Kahsai, TZ, Enders, GC, Gunwar, S, et al. Seminiferous tubule basement membrane. Composition and organization of type IV collagen chains, and the linkage of α3(IV) and α5(IV) chains. J Biol Chem 1997;272:17023–32.Google ScholarPubMed
Gunwar, S, Ballester, F, Noelken, ME, Sado, Y, Ninomiya, Y, Hudson, BG. Glomerular basement membrane. Identification of a novel disulfide-cross-linked network of α3, α4, and α5 chains of type IV collagen and its implications for the pathogenesis of Alport syndrome. J Biol Chem 1998;273:8767–75.Google Scholar
Miner, JH, Sanes, RJ. A network model for the organization of type IV collagen molecules in basement membranes. J Cell Biol 1994;127:879–91.Google Scholar
Kalluri, R, Cosgrove, D. Assembly of type IV collagen. Insights from α3(IV) collagen-deficient mice. J Biol Chem 2000;275:12719–24.Google Scholar
Mok, KW, Mruk, DD, Lee, WM, Cheng, CY. A study to assess the assembly of a functional blood–testis barrier in developing rat testes. Spermatogenesis 2011;1:270–80.Google Scholar
Richardson, LL, Kleinman, HK, Dym, M. Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 1995;52:320–30.Google Scholar
Skinner, MK, Tung, PS, Fritz, IB. Cooperativity between Sertoli cells and testicular peritubular cells in the production and deposition of extracellular matrix components. J Cell Biol 1985;100:1941–7.Google Scholar
Siu, MKY, Lee, WM, Cheng, CY. The interplay of collagen IV, tumor necrosis factor-α, gelatinase B (matrix metalloprotease-9), and tissue inhibitor of metalloprotease-1 in the basal lamina regulates Sertoli cell-tight junction dynamics in the rat testis. Endocrinology 2003;144:371–87.Google Scholar
Lustig, L, Denduchis, B, Gonzalez, NN, Puig, RP. Experimental orchitis induced in rats by passive transfer of an antiserum to seminiferous tubule basement membrane. Arch Androl 1978;1:333–43.Google Scholar
Li, MWM, Xia, W, Mruk, DD, et al. TNFα reversibly disrupts the blood–testis barrier and impairs Sertoli–germ cell adhesion in the seminiferous epithelium of adult rat testes. J Endocrinol 2006;190:313–29.Google Scholar
Wong, EW, Cheng, CY. NC1 domain of collagen alpha3(IV) derived from the basement membrane regulates Sertoli cell blood–testis barrier dynamics. Spermatogenesis 2013;3:e25465.Google Scholar
Su, WH, Cheng, CY. Cdc42 is involved in NC1-peptide regulated BTB dynamics through actin and microtubule cytoskeletal re-organization. FASEB J 2019;33:14461–78.Google Scholar
Gao, Y, Chen, H, Lui, WY, Lee, WM, Cheng, CY. Basement membrane laminin α2 regulation of BTB dynamics via its effects on F-actin and microtubule (MT) cytoskeletons is mediated through mTORC1 signaling. Endocrinology 2017;158:963–78.Google Scholar
Gao, Y, Mruk, D, Chen, H, Lui, WY, Lee, WM, Cheng, CY. Regulation of the blood–testis barrier by a local axis in the testis: role of laminin α2 in the basement membrane. FASEB J 2017;31:584–97.Google Scholar
Meyuhas, O. Ribosomal protein S6 phosphorylation: four decades of research. Int Rev Cell Mol Biol 2015;320:41–73.Google Scholar
Mok, KW, Mruk, DD, Silvestrini, B, Cheng, CY. rpS6 regulates blood–testis barrier dynamics by affecting F-actin organization and protein recruitment. Endocrinology 2012;153:5036–48.Google Scholar
Mok, KW, Mruk, DD, Cheng, CY. rpS6 regulates blood–testis barrier dynamics through Akt-mediated effects on MMP-9. J Cell Sci 2014;127:4870–82.Google Scholar
Mok, KW, Chen, H, Lee, WM, Cheng, CY. rpS6 regulates blood–testis barrier dynamics through Arp3-mediated actin microfilament organization in rat Sertoli cells. An in vitro study. Endocrinology 2015;156:1900–13.Google Scholar
Li, SYT, Yan, M, Chen, H, et al. mTORC1/rpS6 regulates blood–testis barrier (BTB) dynamics and spermatogenetic function in the testis in vivo. Am J Physiol Endocrinol Metab 2018;314:E174–90.Google Scholar
Yan, M, Li, L, Mao, BP, et al. mTORC1/rpS6 signaling complex modifies BTB transport function – an in vivo study using the adjudin model. Am J Physiol Endocrinol Metab 2019;317:E121–38.Google Scholar
Tung, KS, Harakal, J, Qiao, H, et al. Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance. J Clin Invest 2017;127:1046–60.Google Scholar
Russell, LD, Saxena, NK, Weber, JE. Intratesticular injection as a method to assess the potential toxicity of various agents to study mechanisms of normal spermatogenesis. Gamete Res 1987;17:43–56.Google Scholar
Dunleavy, JEM, O’Bryan, MK, Stanton, PG, O’Donnell, L. The cytoskeleton in spermatogenesis. Reproduction 2019;157:R53–72.Google Scholar
Cheng, CY, Mruk, DD. Regulation of spermiogenesis, spermiation and blood–testis barrier dynamics: novel insights from studies on Eps8 and Arp3. Biochem J 2011;435:553–62.Google Scholar
Tang, EI, Mruk, DD, Cheng, CY. Regulation of microtubule (MT)-based cytoskeleton in the seminiferous epithelium during spermatogenesis. Semin Cell Dev Biol 2016;59:35–45.Google Scholar
Ortega, N, Werb, Z. New functional roles for noncollagenous domains of basement membrane collagens. J Cell Sci 2002;115:4201–14.Google Scholar
Sudhakar, A, Boosani, CS. Signaling mechanisms of endogenous angiogenesis inhibitors derived from type IV collagen. Gene Regul Syst Biol 2007;1:217–26.Google Scholar
Assadian, S, Teodoro, JG. Regulation of collagen-derived antiangiogenic factors by p53. Expert Opin Biol Ther 2008;8:941–50.Google Scholar
Barczyk, M, Carracedo, S, Gullberg, D. Integrins. Cell Tissue Res 2010;339:269–80.Google Scholar
Moreno-Layseca, P, Icha, J, Hamidi, H, Ivaska, J. Integrin trafficking in cells and tissues. Nat Cell Biol 2019;21:122–32.Google Scholar
Bachmann, M, Kukkurainen, S, Hytönen, VP, Wehrle-Haller, B. Cell adhesion by integrins. Physiol Rev 2019;99:1655–99.Google Scholar
Dunn, HA, Orlandi, C, Martemyanov, KA. Beyond the ligand: extracellular and transcellular G protein-coupled receptor complexes in physiology and pharmacology. Pharmacol Rev 2019;71:503–19.Google Scholar
Leitinger, B. Discoidin domain receptor functions in physiological and pathological conditions. Int Rev Cell Mol Biol 2014;310:39–87.Google Scholar
de Rooij, DG. The spermatogonial stem cell niche. Microsc Res Tech 2009;72:580–5.Google Scholar
Clermont, Y, Leblond, CP, Messier, B. [Durée du cycle de l’épithélium seminal du rat]. Arch Anat Microsc Morphol Exp 1959;48:37–56.Google Scholar
Hilscher, W. [Beitrage zur Orthologie und Palhologie des “Spermatogoniogenes” der Ratte]. Beitr Pathol Anat 1964;130:69–132.Google Scholar
Franca, LR, Ogawa, T, Avarbock, MR, Brinster, RL, Russell, LD. Germ cell genotype controls cell cycle during spermatogenesis in the rat. Biol Reprod 1998;59:1371–7.Google Scholar
Clermont, Y, Harvey, SC. Duration of the cycle of the seminiferous epithelium of normal, hypophysectomized and hypophysectomized-hormone treated albino rats. Endocrinology 1965;76:80–9.Google Scholar
Russell, LD, Brinster, RL. Ultrastructural observations of spermatogenesis following transplantation of rat testis cells into mouse seminiferous tubules. J Androl 1996;17:615–27.Google Scholar
Aslam, H, Rosiipen, G, Krishnamurthy, H, et al. The cycle duration of the seminiferous epithelium remains unaltered during GnRH antagonist-induced testicular involution in rats and monkeys. J Endocrinol 1999;161:281–8.CrossRefGoogle ScholarPubMed
Leblond, C, Clermont, Y. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann N Y Acad Sci 1952;55:548–73.Google Scholar
Oakberg, EF. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat 1956;99:507–16.Google Scholar
Clermont, Y, Trott, M. Duration of the cycle of the seminiferous epithelium in the mouse and hamster determined by means of 3H-thymidine and radioautography. Fertil Sertil 1969;20:805–17.Google Scholar
Russell, LD, Franca, LR, Brinster, RL. Ultrastructural observations of spermatogenesis in mice resulting from transplantation of mouse spermatogonia. J Androl 1996;17:603–14.Google Scholar
de Rooij, DG, Russell, LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl 2000;21:776–98.Google Scholar
Ehmcke, J, Schlatt, S. A revised model for spermatogonial expansion in man: lessons from non-human primates. Reproduction 2006;132:673–80.Google Scholar
Ehmcke, J, Wistuba, J, Schlatt, S. Spermatogonial stem cells: questions, models and perspectives. Hum Reprod Update 2006;12:275–82.Google Scholar
Heller, CG, Clermont, Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res 1964;20:545–75.Google Scholar
Heller, CG, Clermont, Y. Spermatogenesis in man: an estimate of its duration. Science 1963;140:184–6.Google Scholar
Wu, S, Yan, M, Li, L, et al. mTORC1/rpS6 and spermatogenic function in the testis – insights from the adjudin model. Reprod Toxicol 2019;89:54–66.Google Scholar

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