Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-22T14:06:43.715Z Has data issue: false hasContentIssue false
  • English
  • Français

Modulating oxidative stress and epigenetic homeostasis in preimplantation IVF embryos

Published online by Cambridge University Press:  27 July 2021

Yves Menezo Open the ORCID record for Yves Menezo [Opens in a new window] ,
Patrice Clement ,
Brian Dale Open the ORCID record for Brian Dale [Opens in a new window]  and
Kay Elder
Yves Menezo*
Affiliation:
Laboratoire Clement, Paris, France
Patrice Clement
Affiliation:
Laboratoire Clement, Paris, France
Brian Dale
Affiliation:
Centro Fecondazione Assistita, Napoli, Italy
Kay Elder
Affiliation:
Bourn Hall Clinic, Cambridge, UK
*
Author for correspondence: Yves Menezo. Laboratoire Clement, Paris, France. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Assisted reproductive technology is today considered a safe and reliable medical intervention, with healthy live births a reality for many IVF and ICSI treatment cycles. However, there are increasing numbers of published reports describing epigenetic/imprinting anomalies in children born as a result of these procedures. These anomalies have been attributed to methylation errors in embryo chromatin remodelling during in vitro culture. Here we re-visit three concepts: (1) the so-called ‘in vitro toxicity’ of ‘essential amino acids’ before the maternal to zygotic transition period; (2) the effect of hyperstimulation (controlled ovarian hyperstimulation) on homocysteine in the oocyte environment and the effect on methylation in the absence of essential amino acids; and (3) the fact/postulate that during the early stages of development the embryo undergoes a ‘global’ demethylation. Methylation processes require efficient protection against oxidative stress, which jeopardizes the correct acquisition of methylation marks as well as subsequent methylation maintenance. The universal precursor of methylation [by S-adenosyl methionine (SAM)], methionine, ‘an essential amino acid’, should be present in the culture. Polyamines, regulators of methylation, require SAM and arginine for their syntheses. Cystine, another ‘semi-essential amino acid’, is the precursor of the universal protective antioxidant molecule: glutathione. It protects methylation marks against some undue DNA demethylation processes through ten-eleven translocation (TET), after formation of hydroxymethyl cytosine. Early embryos are unable to convert homocysteine to cysteine as the cystathionine β-synthase pathway is not active. In this way, cysteine is a ‘real essential amino acid’. Most IVF culture medium do not maintain methylation/epigenetic processes, even in mouse assays. Essential amino acids should be present in human IVF medium to maintain adequate epigenetic marking in preimplantation embryos. Furthermore, morphological and morphometric data need to be re-evaluated, taking into account the basic biochemical processes involved in early life.

Keywords

Amino acidsEpigenesisHuman preimplantation embryoImprintingMethylationOxidative stress
Type
Review Article
Information
Zygote , Volume 30 , Issue 2 , April 2022 , pp. 149 - 158
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aguilar, J and Reyley, M (2005). The uterine tubal fluid: secretion, composition and biological effects. Anim Reprod 2, 91–105.Google Scholar
Altmäe, S, Stavreus-Evers, A, Ruiz, JR, Laanpere, M, Syvänen, T, Yngve, A, Salumets, A and Nilsson, TK (2010). Variations in folate pathway genes are associated with unexplained female infertility. Fertil Steril 94, 130–7.Google ScholarPubMed
Aquilano, K, Baldelli, S and Ciriolo, M (2014). Glutathione: new roles in redox signaling for an old antioxidant. Front Pharmacol 5, 196.Google ScholarPubMed
Benkhalifa, M, Montjean, D, Cohen-Bacrie, P and Ménézo, Y (2010). Imprinting: RNA expression homocysteine recycling in the human oocyte. Fertil Steril 93, 1585–90.Google ScholarPubMed
Berker, B, Kaya, C, Aytac, R and Satiroglu, H (2009). Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction. Hum Reprod 24, 2293–302.Google ScholarPubMed
Biggers, JD and Summers, MC (2008). Choosing a culture medium: making informed choices. Fertil Steril 90, 473–83.CrossRefGoogle ScholarPubMed
Bos-Mikich, A, Mattos, AL and Ferrari, AN (2001). Early cleavage of human embryos: an effective method for predicting successful IVF/ICSI outcome. Hum Reprod 12, 2658–6.CrossRefGoogle Scholar
Boxmeer, JC, Steegers-Theunissen, RP, Lindemans, J, Wildhagen, MF, Martini, E, Steegers, EA and Macklon, NS (2008). Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation. Hum Reprod 23, 2570–6.CrossRefGoogle ScholarPubMed
Boxmeer, JC, Macklon, NS, Lindemans, J, Beckers, NG, Eijkemans, MJ, Laven, JS, Steegers, EA and Steegers-Theunissen, RP (2009). IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid. Hum Reprod 24, 1059–66.Google ScholarPubMed
Chatot, CL, Ziomek, CA, Bavister, BD, Lewis, JL and Torres, I (1989). An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro . J Reprod Fertil 86, 679–88.Google ScholarPubMed
Chen, Z, Robbins, KM, Wells, KD and Rivera, RM (2013). Large offspring syndrome: a bovine model for the human loss-of-imprinting overgrowth syndrome Beckwith-Wiedemann. Epigenetics 8, 591–601.Google ScholarPubMed
Choux, C, Binquet, C, Carmignac, V, Bruno, C, Chapusot, C, Barberet, J, Lamotte, M, Sagot, P, Bourc’his, D and Fauque, P (2018). The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility. Hum Reprod 33, 331–40.Google ScholarPubMed
Closs, EI, Simon, A, Vékony, N and Rotmann, A (2004). Plasma membrane transporters for arginine. Nutrition 134(Suppl 10), 2752S–9S.Google Scholar
Cohen, HM, Griffiths, AD, Tawfik, DS and Loakes, D (2005). Determinants of cofactor binding to DNA methyltransferases: insights from a systematic series of structural variants of S-adenosylhomocysteine. Org Biomol Chem 3, 152–61.CrossRefGoogle ScholarPubMed
Comizzoli, P, Urner, F, Sakkas, D and Renard, JP (2003). Up-regulation of glucose metabolism during male pronucleus formation determines the early onset of the S phase in bovine zygotes. Biol Reprod 68, 1934–40.Google Scholar
Croteau, S and Menezo, Y (1994). Methylation in fertilised and parthenogenetic preimplantation mouse embryos. Zygote 2, 47–52.Google ScholarPubMed
Denomme, MM, Zhang, L and Mann, MR (2011). Embryonic imprinting perturbations do not originate from superovulation-induced defects in DNA methylation acquisition. Fertil Steril 96, 734–8.CrossRefGoogle Scholar
Edwards, RG and Ludwig, M (2003). Are major defects in children conceived in vitro due to innate problems in patients or to induced genetic damage? Reprod BioMed Online 7, 131–8.CrossRefGoogle ScholarPubMed
El-Mouatassim, S, Guérin, P and Ménézo, Y (1999). Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation. Mol Hum Reprod 5, 720–5.Google ScholarPubMed
El-Mouatassim, S, Bilotto, S, Russo, GL, Tosti, E and Menezo, Y (2007). APEX/Ref-1 (apurinic/apyrimidic endonuclease DNA-repair gene) expression in human and ascidian (Ciona intestinalis) gametes and embryos. Mol Hum Reprod 13, 549–56.CrossRefGoogle ScholarPubMed
Enciso, M, Sarasa, J, Xanthopoulou, L, Bristow, S, Bowles, M, Fragouli, E, Delhanty, J and Wells, D (2016). Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet 135, 555–68.Google ScholarPubMed
Fenton, HJH (1894). Oxidation of tartaric acid in presence of iron. J Chem Soc Trans 65, 899–910.Google Scholar
Fowler, B (2005). Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. Semin Vasc Med 5, 77–86.CrossRefGoogle ScholarPubMed
Fulka, H, Mrazek, M, Tepla, O and Fulka, J (2004). DNA methylation pattern in human zygotes and developing embryos. Reproduction 128, 703–8.CrossRefGoogle ScholarPubMed
Georgiades, P, Watkins, M, Burton, GJ and Ferguson-Smith, AC (2001). Roles for genomic imprinting and the zygotic genome in placental development. Proc Natl Acad Sci USA 98, 4522–7.Google ScholarPubMed
Greer, EL and Shi, Y (2012). Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 13, 343–57.Google ScholarPubMed
Guérin, P and Ménézo, Y (1995). Hypotaurine and taurine in gamete and embryo environments: de novo synthesis via the cysteine sulfinic acid pathway in oviduct cells. Zygote 3, 333–43.Google ScholarPubMed
Guérin, P, El Mouatassim, S and Ménézo, Y (2001). Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 7, 175–89.CrossRefGoogle ScholarPubMed
Haber, F and Weiss, J (1932). Über die katalyse des hydroperoxydes. [On the catalysis of hydroperoxide]. Naturwissenschaften 20, 948–50.Google Scholar
Haber, F and Willstätter, R (1931). Unpaarigheit und Radikalketten im Reaktion Mechanismus organischer und enzymatischer Vorgänge. Chem Ber 64, 2844–56.CrossRefGoogle Scholar
Hamatani, T, Falco, G, Carter, MG, Akutsu, H, Stagg, CA, Sharov, AA, Dudekula, DB, VanBuren, V and Ko, MS (2004). Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet 13, 2263–78.Google ScholarPubMed
Hattori, H, Hiura, H, Kitamura, A, Miyauchi, N, Kobayashi, N, Takahashi, S, Okae, H, Kyono, K, Kagami, M, Ogata, T and Arima, T (2019). Association of four imprinting disorders and ART. Clin Epigenet 11, 21.Google ScholarPubMed
Hedley, D, Pintilie, M, Woo, J, Nicklee, T, Morrison, A, Birle, D, Fyles, A, Milosevic, M and Hill, R (2004). Up-regulation of the redox mediators thioredoxin and apurinic/apyrimidinic excision (APE)/Ref-1 in hypoxic microregions of invasive cervical carcinomas, mapped using multispectral, wide-field fluorescence image analysis. Am J Pathol 164, 557–6.CrossRefGoogle ScholarPubMed
Herrick, JR, Lyons, SM, Greene-Ermisch, AF, Broeckling, CD, Schoolcraft, WB and Krisher, RL (2018). A carnivore embryo’s perspective on essential amino acids and ammonium in culture medium: effects on the development of feline embryos. Biol Reprod 99, 1070–81.Google ScholarPubMed
Hiura, H, Okae, H, Miyauchi, N, Sato, F, Sato, A, Van De Pette, M, John, RM, Kagami, M, Nakai, K, Soejima, H, Ogata, T and Arima, T (2012). Characterization of DNA methylation errors in patients with disorders conceived by assisted reproduction technologies. Hum Reprod 8, 2541–8.Google Scholar
Ho, Y, Doherty, A and Schultz, R (1994). Mouse preimplantation embryo development in vitro: effect of sodium concentration in culture media on RNA synthesis and accumulation and gene expression. Mol Reprod Dev 38, 131–41.Google ScholarPubMed
Ho, Y, Wigglesworth, K, Eppig, JJ and Schultz, RM (1995). Preimplantation development of mouse embryos in KSOM: augmentation by amino acids and analysis of gene expression. Mol Reprod Dev 41, 232–8.CrossRefGoogle ScholarPubMed
Hoffman, M (2011). Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress. Med Hypotheses 77, 1088–93.CrossRefGoogle ScholarPubMed
Hoffman, DR, Marion, DW, Cornatzer, WE and Duerre, JA (1980). S-Adenosylmethionine and S-adenosylhomocysteine metabolism in isolated rat liver. Effects of l-methionine, l-homocysteine, and adenosine. J Biol Chem 255, 10822–7.CrossRefGoogle ScholarPubMed
Houghton, FD, Hawkhead, JA, Humpherson, PG, Hogg, JE, Balen, AH, Rutherford, AJ and Leese, HJ (2002). Non-invasive amino acid turnover predicts human embryo developmental capacity. Hum Reprod 17, 999–1005.Google ScholarPubMed
Huffman, SR, Pak, Y and Rivera, RM (2015). Superovulation induces alterations in the epigenome of zygotes, and results in differences in gene expression at the blastocyst stage in mice. Mol Reprod Dev 82, 207–17.Google ScholarPubMed
Inoue, A and Zhang, Y (2011). Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334, 194.Google ScholarPubMed
Katari, S, Turan, N, Bibikova, M, Erinle, O, Chalian, R, Foster, M, Gaughan, JP, Coutifaris, C and Sapienza, C (2009). DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet 18, 3769–78Google ScholarPubMed
Kelley, MR and Parsons, SH (2001). Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1. Antioxid Redox Signal 3, 671–83.CrossRefGoogle ScholarPubMed
Kovács, T, Szabó-Meleg, E and Ábrahám, IM (2020). Estradiol-induced epigenetically mediated mechanisms and regulation of gene expression. Int J Mol Sci 21, 3177.CrossRefGoogle ScholarPubMed
Lafontaine, S, Labrecque, R, Palomino, JM, Blondin, P and Sirard, MA (2020). Specific imprinted genes demethylation in association with oocyte donor’s age and culture conditions in bovine embryos assessed at day 7 and 12 post insemination. Theriogenology 158, 321–30.CrossRefGoogle ScholarPubMed
Lane, M and Gardner, DK (1997a). Nonessential amino acids and glutamine decrease the time of the first three cleavage divisions and increase compaction of mouse zygotes in vitro . J Assist Reprod Genet 14, 398–403.Google ScholarPubMed
Lane, M and Gardner, DK (1997b). Differential regulation of mouse embryo development and viability by amino acids. J Reprod Fertil 109, 153–64.Google ScholarPubMed
Lane, M, Hooper, K and Gardner, DK (2001). Effect of essential amino acids on mouse embryo viability and ammonium production. J Assist Reprod Genet 18, 519–25.Google ScholarPubMed
Leese, HJ (1998). Human embryo culture: back to nature. J Assist Reprod Genet 15, 466–8.Google ScholarPubMed
Lefèvre, PL, Palin, MF and Murphy, BD (2011). Polyamines on the reproductive landscape. Endocr Rev 32, 694–712.Google ScholarPubMed
Lu, S, Hoestje, SM, Choo, E and Epner, DE (2003). Induction of caspase dependent and independent apoptosis in response to methionine restriction. Int J Oncol 22, 415–20.Google ScholarPubMed
Manikkam, M, Tracey, R, Guerrero-Bosagna, C and Skinner, MK (2013). Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One 8, e55387.Google ScholarPubMed
Market-Velker, BA, Fernandes, AD and Mann, MR (2010). Side-by-side comparison of five commercial media systems in a mouse model: suboptimal in vitro culture interferes with imprint maintenance. Biol Reprod 83, 938–50.CrossRefGoogle Scholar
Market-Velker, BA, Denomme, MM and Mann, MR (2012). Loss of genomic imprinting in mouse embryos with fast rates of preimplantation development in culture. Biol Reprod 86, 1–16.Google ScholarPubMed
Martín-Romero, FJ, Miguel-Lasobras, EM, Domínguez-Arroyo, JA, González-Carrera, E and Alvarez, IS (2008). Contribution of culture media to oxidative stress and its effect on human oocytes. Reprod Biomed Online 17, 652–61.Google ScholarPubMed
Ménézo, Y and Elder, K (2020). Epigenetic remodeling of chromatin in human ART: addressing deficiencies in culture media. J Assist Reprod Genet 37, 1781–8.CrossRefGoogle ScholarPubMed
Menezo, Y and Laviolette, P (1972). Amino constituents of tubal secretions in the rabbit. Zymogram--proteins--free amino acids. Ann Biol Anim Biochim Biophys 12, 383–96.Google ScholarPubMed
Menezo, Y, Khatchadourian, C, Gharib, A, Hamidi, J, Greenland, T and Sarda, N (1989). Regulation of S-adenosyl methionine synthesis in the mouse embryo. Life Sci 44, 1601–9.Google ScholarPubMed
Menezo, Y Jr, Russo, G, Tosti, E, El Mouatassim, S and Benkhalifa, M (2007). Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays. J Assist Reprod Genet 24, 513–20.Google ScholarPubMed
Ménézo, Y, Lichtblau, I and Elder, K (2013). New insights into human pre-implantation metabolism in vivo and in vitro . J Assist Reprod Genet 30, 293–303.Google ScholarPubMed
Menezo, YJ, Silvestris, E, Dale, B and Elder, K (2016). Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction. Reprod Biomed Online 33, 668–83.Google ScholarPubMed
Menezo, Y, Clément, P and Dale, B (2019a). DNA methylation patterns in the early human embryo and the epigenetic/imprinting problems: a plea for a more careful approach to human assisted reproductive technology (ART). Int J Mol Sci 20, pii: e1342.Google Scholar
Menezo, Y, Dale, B and Elder, K (2019b). The negative impact of the environment on methylation/epigenetic marking in gametes and embryos: a plea for action to protect the fertility of future generations. Mol Reprod Dev 86, 1273–82.CrossRefGoogle ScholarPubMed
Montjean, D, Entezami, F, Lichtblau, I, Belloc, S, Gurgan, T and Menezo, Y (2012). Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells. J Assist Reprod Genet 29, 1221–5.CrossRefGoogle Scholar
Montrose, L, Padmanabhan, V, Goodrich, JM, Domino, SE, Treadwell, MC, Meeker, JD, Watkins, DJ and Dolinoy, DC (2018). Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation. Epigenetics 13, 301–9.Google ScholarPubMed
Morbeck, DE, Krisher, RL, Herrick, JR, Baumann, NA, Matern, D and Moyer, T (2014). Composition of commercial media used for human embryo culture. Fertil Steril 102, 759–66.Google ScholarPubMed
Nahar, MS, Liao, C, Kannan, K, Harris, C and Dolinoy, DC (2015). In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus. Chemosphere 124, 54–60.CrossRefGoogle ScholarPubMed
Nasr-Esfahani, MH, Aitken, JR and Johnson, MH (1990). Hydrogen peroxide levels in mouse oocytes and early cleavage stage embryos developed in vitro or in vivo . Development 109, 501–7.Google ScholarPubMed
Nishimura, K, Nakatsu, F, Kashiwagi, K, Ohno, H, Saito, T and Igarashi, K (2002). Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development. Genes Cells 7, 41–7.Google ScholarPubMed
Ocal, P, Ersoylu, B, Cepni, I, Guralp, O, Atakul, N, Irez, T and Idil, M (2012). The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques. J Assist Reprod Genet 29, 299–304.Google ScholarPubMed
Okamoto, Y, Yoshida, N, Suzuki, T, Shimozawa, N, Asami, M, Matsuda, T, Kojima, N, Perry, AC and Takada, T (2016). DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry. Sci Rep 6, 19134.Google ScholarPubMed
Pabon, JE Jr, Findley, WE and Gibbons, WE (1989).The toxic effect of short exposures to the atmospheric oxygen concentration on early mouse embryonic development. Fertil Steril 51, 896–900.CrossRefGoogle Scholar
Park, JS, Jeong, YS, Shin, ST, Lee, KK and Kang, YK (2007). Dynamic DNA methylation reprogramming: active demethylation and immediate remethylation in the male pronucleus of bovine zygotes. Dev Dyn 236, 2523–33.Google ScholarPubMed
Pegg, AE (2006). Regulation of ornithine decarboxylase. J Biol Chem 281, 14529–32.Google ScholarPubMed
Pendeville, H, Carpino, N, Marine, JC, Takahashi, Y, Muller, M, Martial, JA and Cleveland, JL (2001). The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol Cell Biol 21, 6549–58.CrossRefGoogle ScholarPubMed
Powis, G, Mustacich, D and Coon, A (2000). The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med 29, 312–22.Google ScholarPubMed
Quinn, PJ (1995). Enhanced results in mouse and human embryo culture using a modified human tubal fluid medium lacking glucose and phosphate. J Assist Reprod Genet 12, 97–105.Google ScholarPubMed
Quinn, P, Moinipanah, R, Steinberg, JM and Weathersbee, PS (1995). Successful human in vitro fertilization using a modified human tubal fluid medium lacking glucose and phosphate ions. Fertil Steril 63, 922–4.CrossRefGoogle Scholar
Sato, A, Otsu, E, Negishi, H, Utsunomiya, T and Arima, T (2007). Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod 22, 26–35.Google ScholarPubMed
Servy, EJ, Jacquesson-Fournols, L, Cohen, M and Menezo, YJR (2018). MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet 35, 1431–5.CrossRefGoogle ScholarPubMed
Skinner, MK, Manikkam, M and Guerrero-Bosagna, C (2010). Epigenetic transgenerational actions of environmental factors in disease etiology. Trends Endocrinol Metab 21, 214–22.CrossRefGoogle ScholarPubMed
Smith, ZD, Chan, MM, Humm, KC, Karnik, R, Mekhoubad, S, Regev, A, Eggan, K and Meissner, A (2014). DNA methylation dynamics of the human pre-implantation embryo. Nature 511, 611–5.CrossRefGoogle Scholar
Soda, K (2018). Polyamine metabolism and gene methylation in conjunction with one-carbon metabolism. Int J Mol Sci 19, 3106.CrossRefGoogle ScholarPubMed
Song, S, Ghosh, J, Mainigi, M, Turan, N, Weinerman, R, Truongcao, M, Coutifaris, C and Sapienza, C (2015). DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility. Clin Epigenet 7, 41–8.CrossRefGoogle ScholarPubMed
Summers, MC and Biggers, JD (2003). Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues. Hum Reprod Update 9, 557–82.Google ScholarPubMed
Sunde, A, Brison, D, Dumoulin, J, Harper, J, Lundin, K, Magli, MC, Van den Abbeel, E and Veiga, A (2016). Time to take human embryo culture seriously. Hum Reprod 31, 2174–82.CrossRefGoogle ScholarPubMed
Szymański, W and Kazdepka-Ziemińska, A (2003). Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Ginekol Pol 74, 1392–6.Google ScholarPubMed
Tara, SS, Ghaemimanesh, F, Zarei, S, Reihani-Sabet, F, Pahlevanzadeh, Z, Modarresi, MH and Jeddi-Tehrani, M (2015). Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in male partners of recurrent miscarriage couples. J Reprod Infertil 16, 193–8.Google ScholarPubMed
Tervit, HR, Whittingham, DG and Rowson, LE (1972). Successful culture in vitro of sheep and cattle ova. J Reprod Fertil 30, 493–7.CrossRefGoogle ScholarPubMed
Truong, T and Gardner, DK (2017). Antioxidants improve IVF outcome and subsequent embryo development in the mouse. Hum Reprod 32, 2404–13.Google ScholarPubMed
Wang, L, Zhang, J, Duan, J, Gao, X, Zhu, W, Lu, X, Yang, L, Zhang, J, Li, G, Ci, W, Li, W, Zhou, Q, Aluru, N, Tang, F, He, C, Huang, X and Liu, J (2014). Programming and inheritance of parental DNA methylomes in mammals. Cell 157, 979–91.Google ScholarPubMed
Weiss, J and Humphrey, CW (1949). Reaction between hydrogen peroxide and iron salts. Nature 163, 691.Google Scholar
Young, LE, Sinclair, KD and Wilmut, I (1998). Large offspring syndrome in cattle and sheep. Rev Reprod 3, 155–63.Google ScholarPubMed