1932

Abstract

One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. -adenosylmethionine is a potent aminopropyl and methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA. We propose that 1C metabolism functions as a key biochemical conduit between parental environment and epigenetic regulation of early development and that interindividual and ethnic variability in epigenetic-gene regulation arises because of genetic variants within 1C genes, associated epigenetic regulators, and differentially methylated target DNA sequences. We present evidence to support these propositions, drawing upon studies undertaken in humans and animals. We conclude that future studies should assess the epigenetic effects of cumulative (multigenerational) dietary imbalances contemporaneously in both parents, as this better represents the human experience.

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2019-02-15
2024-04-16
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Literature Cited

  1. 1.  Fleming TP, Watkins AJ, Velazquez MA, Mathers JC, Prentice AM et al. 2018. Origins of lifetime health around the time of conception: causes and consequences. Lancet 391:1842–52
    [Google Scholar]
  2. 2.  Barker DJ, Osmond C 1986. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1:1077–81
    [Google Scholar]
  3. 3.  Sinclair KD, Watkins AJ 2013. Parental diet, pregnancy outcomes and offspring health: metabolic determinants in developing oocytes and embryos. Reprod. Fertil. Dev. 26:99–114
    [Google Scholar]
  4. 4.  Albertini D, Evers JL, Geraedts JP, Gianaroli L, Sharpe R et al. 2014. Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report. J. Assist. Reprod. Genet. 31:947–58
    [Google Scholar]
  5. 5.  Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A et al. 2017. Metabolism disrupting chemicals and metabolic disorders. Reprod. Toxicol. 68:3–33
    [Google Scholar]
  6. 6.  Sinclair KD, Rutherford KM, Wallace JM, Brameld JM, Stöger R et al. 2016. Epigenetics and developmental programming of welfare and production traits in farm animals. Reprod. Fertil. Dev. 28:1443–78
    [Google Scholar]
  7. 7.  Gilbert SF, Bosch TC, Ledón-Rettig C 2015. Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents. Nat. Rev. Genet. 16:611–22
    [Google Scholar]
  8. 8.  Manjrekar J 2017. Epigenetic inheritance, prions and evolution. J. Genet. 96:445–56
    [Google Scholar]
  9. 9.  Sharma U, Rando OJ 2017. Metabolic inputs into the epigenome. Cell Metab 25:544–58
    [Google Scholar]
  10. 10.  Xu J, Sinclair KD 2015. One-carbon metabolism and epigenetic regulation of embryo development. Reprod. Fertil. Dev. 27:667–76
    [Google Scholar]
  11. 11.  Stover PJ 2009. One-carbon metabolism–genome interactions in folate-associated pathologies. J. Nutr. 139:2402–5
    [Google Scholar]
  12. 12.  Stover PJ, Field MS 2011. Trafficking of intracellular folates. Adv. Nutr. 2:325–31
    [Google Scholar]
  13. 13.  Lucock M 2000. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol. Genet. Metab. 71:121–38
    [Google Scholar]
  14. 14.  Ducker GS, Rabinowitz JD 2017. One-carbon metabolism in health and disease. Cell Metab 25:27–42
    [Google Scholar]
  15. 15.  Mason JB 2003. Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J. Nutr. 3:941S–47S
    [Google Scholar]
  16. 16.  Garratt LC, Ortori CA, Tucker GA, Stablitzky F, Bennett MJ, Barrett DA 2005. Comprehensive metabolic profiling of mono- and polyglutamated folates and their precursors in plant and animal tissue using liquid chromatography/negative ion electrospray ionisation tandem mass spectrometry. Rapid Commun. Mass Spectrom. 19:2390–98
    [Google Scholar]
  17. 17.  Visentin M, Diop-Bove N, Zhao R, Goldman ID 2014. The intestinal absorption of folates. Annu. Rev. Physiol. 76:251–74
    [Google Scholar]
  18. 18.  Zhao R, Matherly LH, Goldman ID 2009. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev. Mol. Med. 28:1–28
    [Google Scholar]
  19. 19.  Shane B 2008. Folate and vitamin B12 metabolism: overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr. Bull. 29:S5–16
    [Google Scholar]
  20. 20.  Mentch SJ, Locasale JW 2016. One-carbon metabolism and epigenetics: understanding the specificity. Ann. N.Y. Acad. Sci. 1363:91–98
    [Google Scholar]
  21. 21.  Škovierová H, Vidomanová E, Mahmood S, Sopková J, Drgová A et al. 2016. The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int. J. Mol. Sci. 17:1–18
    [Google Scholar]
  22. 22.  Gaughan DJ, Kluijtmans LA, Barbaux S, McMaster D, Young IS et al. 2001. The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Atherosclerosis 157:451–56
    [Google Scholar]
  23. 23.  Ho V, Massey TE, King WD 2013. Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism. Genes Nutr 8:571–80
    [Google Scholar]
  24. 24.  Finkelstein JD, Martin JJ 1984. Methionine metabolism in mammals: distribution of homocysteine between competing pathways. J. Biol. Chem. 259:9508–13
    [Google Scholar]
  25. 25.  Li F, Feng Q, Lee C, Wang S, Pelleymounter LL et al. 2008. Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization. Mol. Genet. Metab. 94:326–35
    [Google Scholar]
  26. 26.  Roje S 2006. S-Adenosyl-l-methionine: beyond the universal methyl group donor. Phytochemistry 67:1686–98
    [Google Scholar]
  27. 27.  Ulrey CL, Liu L, Andrews LG, Tollefsbol TO 2005. The impact of metabolism on DNA methylation. Hum. Mol. Genet. 14:R139–47
    [Google Scholar]
  28. 28.  Caudill MA, Wang JC, Melnyk S, Pogribny IP, Jernigan S et al. 2001. Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine β-synthase heterozygous mice. J. Nutr. 131:2811–18
    [Google Scholar]
  29. 29.  Selhub J 1999. Homocysteine metabolism. Annu. Rev. Nutr. 19:217–46
    [Google Scholar]
  30. 30.  Tretter L, Patocs A, Chinopoulos C 2016. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochim. Biophys. Acta 1857:1086–101
    [Google Scholar]
  31. 31.  Ballhausen D, Mittaz L, Boulat O, Bonafé L, Braissant O 2009. Evidence for catabolic pathway of propionate metabolism in CNS: expression pattern of methylmalonyl-CoA mutase and propionyl-CoA carboxylase alpha-subunit in developing and adult rat brain. Neuroscience 164:578–87
    [Google Scholar]
  32. 32.  De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Bäckhed F, Mithieux G 2016. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab 24:151–57
    [Google Scholar]
  33. 33.  Mendonça N, Granic A, Mathers JC, Martin-Ruiz C, Wesnes KA et al. 2017. One-carbon metabolism biomarkers and cognitive decline in the very old: the Newcastle 85+ Study. J. Am. Med. Dir. Assoc. 18:806.e19–e27
    [Google Scholar]
  34. 34.  Pegg AE 2006. Regulation of ornithine decarboxylase J. Biol. . Chem 281:14529–32
    [Google Scholar]
  35. 35.  Gamble LD, Hogarty MD, Liu X, Ziegler DS, Marshall G et al. 2012. Polyamine pathway inhibition as a novel therapeutic approach to treating neuroblastoma. Front. Oncol. 162:1–10
    [Google Scholar]
  36. 36.  Pegg AE 2016. Functions of polyamines in mammals. J. Biol. Chem. 291:14904–12
    [Google Scholar]
  37. 37.  Vance DE 2013. Physiological roles of phosphatidylethanolamine N-methyltransferase. Biochim. Biophys. Acta 1831:626–32
    [Google Scholar]
  38. 38.  Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE 2007. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim. Biophys. Acta 1771:654–62
    [Google Scholar]
  39. 39.  Wright MM, Howe AG, Zaremberg V 2004. Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. Biochem. Cell Biol. 82:18–26
    [Google Scholar]
  40. 40.  Shuvalov O, Petukhov A, Daks A, Fedorova O, Vasileva E, Barlev NA 2017. One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy. Oncotarget 8:23955–77
    [Google Scholar]
  41. 41.  Crider KS, Bailey LB, Berry RJ 2011. Folic acid food fortification—its history, effect, concerns, and future directions. Nutrients 3:370–84
    [Google Scholar]
  42. 42.  Smith AD, Refsum H 2016. Homocysteine, B vitamins, and cognitive impairment. Annu. Rev. Nutr. 17:211–39
    [Google Scholar]
  43. 43.  McLean E, de Benoist B, Allen LH 2008. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr. Bull. 29:S38–51
    [Google Scholar]
  44. 44.  Brito A, Mujica-Coopman MF, López de Romaña D, Cori H, Allen LH 2015. Folate and vitamin B12 status in Latin America and the Caribbean: an update. Food Nutr. Bull. 36:S109–18
    [Google Scholar]
  45. 45.  Soofi S, Khan GN, Sadiq K, Ariff S, Habib A et al. 2017. Prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data. BMJ Open 7:e018007
    [Google Scholar]
  46. 46.  Gilsing AM, Crowe FL, Lloyd-Wright Z, Sanders TA, Appleby PN et al. 2010. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Eur. J. Clin. Nutr. 64:933–39
    [Google Scholar]
  47. 47.  Steegers-Theunissen RP, Twigt J, Pestinger V, Sinclair KD 2013. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum. Reprod. Update 19:640–55
    [Google Scholar]
  48. 48.  Obeid R, Murphy M, Solé-Navais P, Yajnik C 2017. Cobalamin status from pregnancy to early childhood: lessons from global experience. Adv. Nutr. 8:971–79
    [Google Scholar]
  49. 49.  Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao S et al. 2008. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia 51:29–38
    [Google Scholar]
  50. 50.  Scott JM, Weir DG 1981. The methyl folate trap: a physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet 2:337–40
    [Google Scholar]
  51. 51.  Palmer AM, Kamynina E, Field MS, Stover PJ 2017. Folate rescues vitamin B12 depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability. PNAS 114:E4095–102
    [Google Scholar]
  52. 52.  Jing M, Rech L, Wu Y, Goltz D, Taylor CG, House JD 2015. Effects of zinc deficiency and zinc supplementation on homocysteine levels and related enzyme expression in rats. J. Trace Elem. Med. Biol. 30:77–82
    [Google Scholar]
  53. 53.  Suttle N 2010. Cobalt. Mineral Nutrition of Livestock S Hulbert, K Hill 223–54 Wallingford, UK: CAB Int
    [Google Scholar]
  54. 54.  Sutherland RJ, Cordes DO, Carthew GC 1979. Ovine white liver disease—an hepatic dysfunction associated with vitamin B12 deficiency. N.Z. Vet. J. 27:227–32
    [Google Scholar]
  55. 55.  Kennedy DG, Kennedy S, Blanchflower WJ, Scott JM, Weir DG et al. 1994. Cobalt-vitamin B12 deficiency causes accumulation of odd-numbered, branched-chain fatty acids in the tissues of sheep. Br. J. Nutr. 71:67–76
    [Google Scholar]
  56. 56.  Quirk MF, Norton BW 1987. The relationship between the cobalt nutrition of ewes and the vitamin B12 status of ewes and their lambs. Aust. J. Agric. Res. 38:1071–82
    [Google Scholar]
  57. 57.  O'Harte FP, Kennedy DG, Blanchflower WJ, Rice DA 1989. Methylmalonic acid in the diagnosis of cobalt deficiency in barley-fed lambs. Br. J. Nutr. 62:729–38
    [Google Scholar]
  58. 58.  Shahsavari A, D'Occhio MJ, Al Jassim R 2016. The role of rumen-protected choline in hepatic function and performance of transition dairy cows. Br. J. Nutr. 116:35–44
    [Google Scholar]
  59. 59.  Corbin KD, Zeisel SH 2012. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr. Opin. Gastroenterol. 28:159–65
    [Google Scholar]
  60. 60.  Cole LK, Vance JE, Vance DE 2012. Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochim. Biophys. Acta 1821:754–61
    [Google Scholar]
  61. 61.  Zeisel SH 2006. Choline: critical role during fetal development and dietary requirements in adults. Annu. Rev. Nutr. 26:229–50
    [Google Scholar]
  62. 62.  Zeisel SH 2011. What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders. Mol. Neurobiol. 44:185–91
    [Google Scholar]
  63. 63.  Tacconi M, Wurtman RJ 1985. Phosphatidylcholine produced in rat synaptosomes by N-methylation is enriched in polyunsaturated fatty acids. PNAS 82:4828–31
    [Google Scholar]
  64. 64.  DeLong CJ, Shen YJ, Thomas MJ, Cui Z 1999. Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. J. Biol. Chem. 274:29683–88
    [Google Scholar]
  65. 65.  Dawson SL, Bowe SJ, Crowe TC 2016. A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: a meta-analysis. Nutr. Res. 36:499–508
    [Google Scholar]
  66. 66.  Christensen KE, Wu Q, Wang X, Deng L, Caudill MA, Rozen R 2010. Steatosis in mice is associated with gender, folate intake, and expression of genes of one-carbon metabolism. J. Nutr. 140:1736–41
    [Google Scholar]
  67. 67.  Eussen SJ, Nilsen RM, Midttun Ø, Hustad S, IJssennagger N et al. 2013. North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. Br. J. Nutr. 110:363–74
    [Google Scholar]
  68. 68.  Michels KA, Wactawski-Wende J, Mills JL, Schliep KC, Gaskins AJ et al. 2017. Folate, homocysteine and the ovarian cycle among healthy regularly menstruating women. Hum. Reprod. 32:1743–50
    [Google Scholar]
  69. 69.  Fischer LM, daCosta KA, Kwock L, Stewart PW, Lu TS et al. 2007. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am. J. Clin. Nutr. 85:1275–85
    [Google Scholar]
  70. 70.  Resseguie M, Song J, Niculescu MD, da Costa KA, Randall TA, Zeisel SH 2007. Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogenin human and mouse primary hepatocytes. FASEB J 21:2622–32
    [Google Scholar]
  71. 71.  Hao H, d'Alincourt-Salazar M, Kelley KM, Shatnawi A, Mukherjee S et al. 2007. Estrogen-induced and TAFII30-mediated gene repression by direct recruitment of the estrogen receptor and co-repressors to the core promoter and its reversal by tamoxifen. Oncogene 26:7872–84
    [Google Scholar]
  72. 72.  Corbin JM, Ruiz-Echevarría MJ 2016. One-carbon metabolism in prostate cancer: the role of androgen signaling. Int. J. Mol. Sci. 17:E1208
    [Google Scholar]
  73. 73.  Jin B, Li Y, Robertson KD 2011. DNA methylation: Superior or subordinate in the epigenetic hierarchy?. Genes Cancer 2:607–17
    [Google Scholar]
  74. 74.  Hemberger M, Dean W, Reik W 2009. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal. Nat. Rev. Mol. Cell Biol. 10:526–37
    [Google Scholar]
  75. 75.  Anderson OS, Sant KE, Dolinoy DC 2012. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J. Nutr. Biochem. 23:853–59
    [Google Scholar]
  76. 76.  Kareta MS, Botello ZM, Ennis JJ, Chou C, Chédin F 2006. Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. J. Biol. Chem. 281:25893–902
    [Google Scholar]
  77. 77.  Murín R, Vidomanová E, Kowtharapu BS, Hatok J, Dobrota D 2017. Role of S-adenosylmethionine cycle in carcinogenesis. Gen. Physiol. Biophys. 36:513–20
    [Google Scholar]
  78. 78.  Portela A, Esteller M 2010. Epigenetic modifications and human disease. Nat. Biotechnol. 28:1057–68
    [Google Scholar]
  79. 79.  Jin B, Robertson KD 2013. DNA methyltransferases, DNA damage repair, and cancer. Adv. Exp. Med. Biol. 754:3–29
    [Google Scholar]
  80. 80.  Chedin F, Lieber MR, Hsieh CL 2002. The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. PNAS 99:16916–21
    [Google Scholar]
  81. 81.  Hata K, Okano M, Lei H, Li E 2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–93
    [Google Scholar]
  82. 82.  Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL et al. 2006. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311:395–98
    [Google Scholar]
  83. 83.  Lim DH, Maher ER 2010. Genomic imprinting syndromes and cancer. Adv. Genet. 70:145–75
    [Google Scholar]
  84. 84.  Jeziorska DM, Murray RJS, De Gobbi M, Gaentzsch R, Garrick D et al. 2017. DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. PNAS 114:E7526–35
    [Google Scholar]
  85. 85.  Deaton AM, Bird A 2011. CpG islands and the regulation of transcription. Genes Dev 25:1010–22
    [Google Scholar]
  86. 86.  Ziller MJ, Müller F, Liao J, Zhang Y, Gu H et al. 2011. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLOS Genet 7:e1002389
    [Google Scholar]
  87. 87.  Jang HS, Shin WJ, Lee JE, Do JT 2017. CpG and non-CpG methylation in epigenetic gene regulation and brain function. Genes 8:E148
    [Google Scholar]
  88. 88.  Smith ZD, Meissner A 2013. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14:204–20
    [Google Scholar]
  89. 89.  Barrès R, Osler ME, Yan J, Rune A, Fritz T et al. 2009. Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density. Cell Metab 10:189–98
    [Google Scholar]
  90. 90.  Zhang D, Wu B, Wang P, Wang Y, Lu P et al. 2017. Non-CpG methylation by DNMT3B facilitates REST binding and gene silencing in developing mouse hearts. Nucleic Acids Res 45:3102–15
    [Google Scholar]
  91. 91.  Groot GS, Kroon AM 1979. Mitochondrial DNA from various organisms does not contain internally methylated cytosine in -CCGG- sequences. Biochim. Biophys. Acta 564:355–57
    [Google Scholar]
  92. 92.  Maekawa M, Taniguchi T, Higashi H, Sugimura H, Sugano K, Kanno T 2004. Methylation of mitochondrial DNA is not a useful marker for cancer detection. Clin. Chem. 50:1480–81
    [Google Scholar]
  93. 93.  Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM 2011. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. PNAS 108:3630–35
    [Google Scholar]
  94. 94.  Bellizzi D, D'Aquila P, Scafone T, Giordano M, Riso V et al. 2013. The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern. DNA Res 20:537–47
    [Google Scholar]
  95. 95.  van der Wijst MG, van Tilburg AY, Ruiters MH, Rots MG 2017. Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression. Sci. Rep. 7:177
    [Google Scholar]
  96. 96.  Morera L, Lübbert M, Jung M 2016. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin. Epigenet. 8:57
    [Google Scholar]
  97. 97.  Lan F, Shi Y 2009. Epigenetic regulation: methylation of histone and non-histone proteins. Sci. China C Life Sci. 52:311–22
    [Google Scholar]
  98. 98.  Ng SS, Yue WW, Oppermann U, Klose RJ 2009. Dynamic protein methylation in chromatin biology. Cell. Mol. Life Sci. 66:407–22
    [Google Scholar]
  99. 99.  Bannister AJ, Schneider R, Kouzarides T 2002. Histone methylation: Dynamic or static?. Cell 109:801–6
    [Google Scholar]
  100. 100.  Barski A, Cuddapah S, Cui K, Roh TY, Schones DE et al. 2007. High-resolution profiling of histone methylations in the human genome. Cell 129:823–37
    [Google Scholar]
  101. 101.  Amort T, Rieder D, Wille A, Khokhlova-Cubberley D, Riml C et al. 2017. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biol 18:1
    [Google Scholar]
  102. 102.  Willyard C 2017. An epigenetics gold rush: new controls for gene expression. Nature 542:406–8
    [Google Scholar]
  103. 103.  Lee M, Kim B, Kim VN 2014. Emerging roles of RNA modification: m6A and U-tail. Cell 158:980–87
    [Google Scholar]
  104. 104.  Yue Y, Liu J, He C 2015. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev 29:1343–55
    [Google Scholar]
  105. 105.  Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z et al. 2017. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 543:573–76
    [Google Scholar]
  106. 106.  Szyf M, Tang YY, Hill KG, Musci R 2016. The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion. Transl. Behav. Med. 6:55–62
    [Google Scholar]
  107. 107.  Gillette TG, Hill JA 2015. Readers, writers, and erasers: chromatin as the whiteboard of heart disease. Circ. Res. 116:1245–53
    [Google Scholar]
  108. 108.  Kohli RM, Zhang Y 2013. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502:472–79
    [Google Scholar]
  109. 109.  Batista PJ 2017. The RNA modification N6-methyladenosine and its implications in human disease. Genom. Proteom. Bioinform. 15:154–63
    [Google Scholar]
  110. 110.  Waterland RA, Jirtle RL 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23:5293–300
    [Google Scholar]
  111. 111.  Waterland RA, Kellermayer R, Laritsky E, Rayco-Solon P, Harris RA et al. 2010. Season of conception in rural Gambia affects DNA methylation at putative human metastable epialleles. PLOS Genet 6:e1001252
    [Google Scholar]
  112. 112.  Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE et al. 2014. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat. Commun. 5:3746
    [Google Scholar]
  113. 113.  Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S et al. 2007. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. PNAS 104:19351–56
    [Google Scholar]
  114. 114.  Maloney CA, Hay SM, Young LE, Sinclair KD, Rees WD 2011. A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. J. Nutr. 141:95–100
    [Google Scholar]
  115. 115.  Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP 2000. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127:4195–202
    [Google Scholar]
  116. 116.  Watkins AJ, Wilkins A, Cunningham C, Perry VH, Seet MJ et al. 2008. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J. Physiol. 586:2231–44
    [Google Scholar]
  117. 117.  Rees WD 2002. Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. Proc. Nutr. Soc. 61:71–77
    [Google Scholar]
  118. 118.  Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC 2005. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J. Nutr. 135:1382–86
    [Google Scholar]
  119. 119.  Altobelli G, Bogdarina IG, Stupka E, Clark AJ, Langley-Evans S 2013. Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid. PLOS ONE 8:e82989
    [Google Scholar]
  120. 120.  Carone BR, Fauquier L, Habib N, Shea JM, Hart CE et al. 2010. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–96
    [Google Scholar]
  121. 121.  Watkins AJ, Sinclair KD 2014. Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice. Am. J. Physiol. Heart Circ. Physiol. 306:H1444–52
    [Google Scholar]
  122. 122.  Watkins AJ, Sirovica S, Stokes B, Isaacs M, Addison O, Martin RA 2017. Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice. Biochim. Biophys. Acta 1863:1371–81
    [Google Scholar]
  123. 123.  Lambrot R, Xu C, Saint-Phar S, Chountalos G, Cohen T et al. 2013. Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat. Commun. 4:2889
    [Google Scholar]
  124. 124.  Dolinoy DC, Huang D, Jirtle RL 2007. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. PNAS 104:13056–61
    [Google Scholar]
  125. 125.  Mao Z, Xia W, Huo W, Zheng T, Bassig BA et al. 2017. Pancreatic impairment and Igf2 hypermethylation induced by developmental exposure to bisphenol A can be counteracted by maternal folate supplementation. J. Appl. Toxicol. 37:825–35
    [Google Scholar]
  126. 126.  Liu H, Wang J, Mou D, Che L, Fang Z et al. 2017. Maternal methyl donor supplementation during gestation counteracts the bisphenol A-induced impairment of intestinal morphology, disaccharidase activity, and nutrient transporters gene expression in newborn and weaning pigs. Nutrients 9:E423
    [Google Scholar]
  127. 127.  Mínguez-Alarcón L, Gaskins AJ, Chiu YH, Souter I, Williams PL et al. 2016. Dietary folate intake and modification of the association of urinary bisphenol A concentrations with in vitro fertilization outcomes among women from a fertility clinic. Reprod. Toxicol. 65:104–12
    [Google Scholar]
  128. 128.  Lea RG, Amezaga MR, Loup B, Mandon-Pépin B, Stefansdottir A et al. 2016. The fetal ovary exhibits temporal sensitivity to a “real-life” mixture of environmental chemicals. Sci. Rep. 6:22279
    [Google Scholar]
  129. 129.  Drake AJ, O'Shaughnessy PJ, Bhattacharya S, Monteiro A, Kerrigan D et al. 2015. In utero exposure to cigarette chemicals induced sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver. BMC Med 13:18
    [Google Scholar]
  130. 130.  Parisi F, Rousian M, Koning AH, Willemsen SP, Cetin I et al. 2017. Periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth trajectories: the Rotterdam Periconceptional Cohort (Predict Study). Fertil. Steril. 107:691–98
    [Google Scholar]
  131. 131.  Gaskins AJ, Chavarro JE 2018. Diet and fertility: a review. Am. J. Obstet. Gynecol. 218:379–89
    [Google Scholar]
  132. 132.  Pront R, Margalioth EJ, Green R, Eldar-Geva T, Maimoni Z et al. 2009. Prevalence of low serum cobalamin in infertile couples. Andrologia 41:46–50
    [Google Scholar]
  133. 133.  Haggarty P, McCallum H, McBain H, Andrews K, Duthie S et al. 2006. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet 367:1513–19
    [Google Scholar]
  134. 134.  Gaskins AJ, Afeiche MC, Wright DL, Toth TL, Williams PL et al. 2014. Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet. Gynecol. 124:801–9
    [Google Scholar]
  135. 135.  Grace KS, Sinclair KD 2009. Assisted reproductive technology, epigenetics, and long-term health: a developmental time bomb still ticking. Semin. Reprod. Med. 27:409–16
    [Google Scholar]
  136. 136.  van Montfoort AP, Hanssen LL, de Sutter P, Viville S, Geraedts JP, de Boer P 2012. Assisted reproduction treatment and epigenetic inheritance. Hum. Reprod. Update 18:171–97
    [Google Scholar]
  137. 137.  Canovas S, Ivanova E, Romar R, García-Martínez S, Soriano-Úbeda C et al. 2017. DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids. eLife 6:e23670
    [Google Scholar]
  138. 138.  Vermeiden JP, Bernardus RE 2013. Are imprinting disorders more prevalent after human in vitro fertilization or intracytoplasmic sperm injection?. Fertil. Steril. 99:642–51
    [Google Scholar]
  139. 139.  Young LE, Sinclair KD, Wilmut I 1998. Large offspring syndrome in cattle and sheep. Rev. Reprod. 3:155–63
    [Google Scholar]
  140. 140.  Sinclair KD, Young LE, Wilmut I, McEvoy TG 2000. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men. Hum. Reprod. 15:68–86
    [Google Scholar]
  141. 141.  Weksberg R, Shuman C, Beckwith JB 2010. Beckwith-Wiedemann syndrome. Eur. J. Hum. Genet. 18:8–14
    [Google Scholar]
  142. 142.  Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG et al. 2001. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat. Genet. 27:153–54
    [Google Scholar]
  143. 143.  Sinclair KD, McEvoy TG, Maxfield EK, Maltin CA, Young LE et al. 1999. Aberrant fetal growth and development after in vitro culture of sheep zygotes. J. Reprod. Fertil. 116:177–86
    [Google Scholar]
  144. 144.  Rooke JA, McEvoy TG, Ashworth CJ, Robinson JJ, Wilmut I et al. 2007. Ovine fetal development is more sensitive to perturbation by the presence of serum in embryo culture before rather than after compaction. Theriogenology 67:639–47
    [Google Scholar]
  145. 145.  Rooke JA, Anderson J, Staines ME, Sinclair KD 2003. Quantification of S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) in bovine granulosa cells (BGC) and blastocysts under differing cultural conditions. Reprod. Abstr. Ser. 30:68–69
    [Google Scholar]
  146. 146.  Chen Z, Robbins KM, Wells KD, Rivera RM 2013. Large offspring syndrome: a bovine model for the human loss-of-imprinting overgrowth syndrome Beckwith-Wiedemann. Epigenetics 8:591–601
    [Google Scholar]
  147. 147.  Chen Z, Hagen DE, Elsik CG, Ji T, Morris CJ et al. 2015. Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction. PNAS 112:4618–23
    [Google Scholar]
  148. 148.  Chen Z, Hagen DE, Ji T, Elsik CG, Rivera RM 2017. Global misregulation of genes largely uncoupled to DNA methylome epimutations characterizes a congenital overgrowth syndrome. Sci. Rep. 7:12667
    [Google Scholar]
  149. 149.  Boxmeer JC, Steegers-Theunissen RP, Lindemans J, Wildhagen MF, Martini E et al. 2008. Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation. Hum. Reprod. 23:2570–76
    [Google Scholar]
  150. 150.  Kanakkaparambil R, Singh R, Li D, Webb R, Sinclair KD 2009. B-vitamin and homocysteine status determines ovarian response to gonadotropin treatment in sheep. Biol. Reprod. 80:743–52
    [Google Scholar]
  151. 151.  Twigt JM, Hammiche F, Sinclair KD, Beckers NG, Visser JA et al. 2011. Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation. J. Clin. Endocrinol. Metab. 96:E322–29
    [Google Scholar]
  152. 152.  Anckaert E, Romero S, Adriaenssens T, Smitz J 2010. Effects of low methyl donor levels in culture medium during mouse follicle culture on oocyte imprinting establishment. Biol. Reprod. 83:377–86
    [Google Scholar]
  153. 153.  O'Neil C 1998. Endogenous folic acid is essential for normal development of preimplantation embryos. Hum. Reprod. 13:1312–16
    [Google Scholar]
  154. 154.  Kwong WY, Adamiak SJ, Gwynn A, Singh R, Sinclair KD 2010. Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo. Reproduction 139:705–15
    [Google Scholar]
  155. 155.  Shojaei Saadi HA, Gagné D, Fournier É, Baldoceda Baldeon LM, Sirard MA, Robert C 2016. Responses of bovine early embryos to S-adenosyl methionine supplementation in culture. Epigenomics 8:1039–60
    [Google Scholar]
  156. 156.  Ho V, Ashbury JE, Taylor S, Vanner S, King WD 2015. Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk. Mutat. Res. 782:1–6
    [Google Scholar]
  157. 157.  Huidobro C, Toraño EG, Fernández AF, Urdinguio RG, Rodríguez RM et al. 2013. A DNA methylation signature associated with the epigenetic repression of glycine N-methyltransferase in human hepatocellular carcinoma. J. Mol. Med. 91:939–50
    [Google Scholar]
  158. 158.  Gong M, Dong W, He T, Shi Z, Huang G et al. 2015. MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies. PLOS ONE 10:e0121147
    [Google Scholar]
  159. 159.  Cao Y, Xu J, Zhang Z, Huang X, Zhang A et al. 2013. Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis. Gene 514:105–11
    [Google Scholar]
  160. 160.  Yan L, Zhao L, Long Y, Zou P, Ji G et al. 2012. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offspring: evidence from 25 case-control studies. PLOS ONE 7:e41689
    [Google Scholar]
  161. 161.  Cyril C, Rai P, Chandra N, Gopinath PM, Satyamoorthy K 2009. MTHFR gene variants C677T, A1298C and association with Down syndrome: a case-control study from South India. Indian J. Hum. Genet. 15:60–64
    [Google Scholar]
  162. 162.  Kaur A, Kaur A 2016. Maternal MTHFR polymorphism (677 C-T) and risk of Down's syndrome child: meta-analysis. J. Genet. 95:505–13
    [Google Scholar]
  163. 163.  Lucock M, Yates Z 2005. Folic acid: Vitamin and panacea or genetic time bomb?. Nat. Rev. Genet. 6:235–40
    [Google Scholar]
  164. 164.  Friso S, Choi SW 2002. Gene-nutrient interactions and DNA methylation. J. Nutr. 132:2382S–87S
    [Google Scholar]
  165. 165.  Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML 1999. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat. Struct. Biol. 6:359–65
    [Google Scholar]
  166. 166.  McNulty H, Dowey LRC, Strain JJ, Dunne A, Ward M et al. 2006. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C→T polymorphism. Circulation 113:74–80
    [Google Scholar]
  167. 167.  Gris JC, Quéré I, Monpeyroux F, Mercier E, Ripart-Neveu S et al. 1999. Case-control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent—the Nîmes Obstetricians and Haematologists Study5 (NOHA5). Thromb. Haemost. 81:891–99
    [Google Scholar]
  168. 168.  Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG et al. 2002. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. PNAS 99:5606–11
    [Google Scholar]
  169. 169.  de Bree A, van Dusseldorp M, Brouwer IA, van het Hof KH, Steegers-Theunissen RP 1997. Folate intake in Europe: recommended, actual and desired intake. Eur. J. Clin. Nutr. 51:643–60
    [Google Scholar]
  170. 170.  Park JY, Nicolas G, Freisling H, Biessy C, Scalbert A et al. 2012. Comparison of standardised dietary folate intake across ten countries participating in the European Prospective Investigation into Cancer and Nutrition. Br. J. Nutr. 108:552–69
    [Google Scholar]
  171. 171.  Khoshnood B, Loane M, de Walle H, Arriola L, Addor MC et al. 2015. Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ 351:h5949
    [Google Scholar]
  172. 172.  Chen Z, Karaplis AC, Ackerman SL, Pogribny IP, Melnyk S et al. 2001. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum. Mol. Genet. 10:433–43
    [Google Scholar]
  173. 173.  Kelly TL, Neaga OR, Schwahn BC, Rozen R, Trasler JM 2005. Infertility in 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient male mice is partially alleviated by lifetime dietary betaine supplementation. Biol. Reprod. 72:667–77
    [Google Scholar]
  174. 174.  Chan D, Cushnie DW, Neaga OR, Lawrance AK, Rozen R, Trasler JM 2010. Strain-specific defects in testicular development and sperm epigenetic patterns in 5,10-methylenetetrahydrofolate reductase-deficient mice. Endocrinology 151:3363–73
    [Google Scholar]
  175. 175.  Li E, Bestor TH, Jaenisch R 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–26
    [Google Scholar]
  176. 176.  Okano M, Bell DW, Haber DA, Li E 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–57
    [Google Scholar]
  177. 177.  Shirohzu H, Kubota T, Kumazawa A, Sado T, Chijiwa T et al. 2002. Three novel DNMT3B mutations in Japanese patients with ICF syndrome. Am. J. Med. Genet. 112:31–37
    [Google Scholar]
  178. 178.  Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH 2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–39
    [Google Scholar]
  179. 179.  Shen W, Krautscheid P, Rutz AM, Bayrak-Toydemir P, Dugan SL 2018. De novo loss-of-function variants of ASH1L are associated with an emergent neurodevelopmental disorder. Eur. J. Med. Genet. S1769–7212:30878–79
    [Google Scholar]
  180. 180.  Blackburn PR, Tischer A, Zimmermann MT, Kemppainen JL, Sastry S et al. 2017. A novel Kleefstra syndrome-associated variant that affects the conserved TPLX motif within the ankyrin repeat of EHMT1 leads to abnormal protein folding. J. Biol. Chem. 292:3866–76
    [Google Scholar]
  181. 181.  Balemans MC, Ansar M, Oudakker AR, van Caam AP, Bakker B et al. 2014. Reduced euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice. Dev. Biol. 386:395–407
    [Google Scholar]
  182. 182.  Gertz J, Varley KE, Reddy TE, Bowling KM, Pauli F et al. 2011. Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation. PLOS Genet 7:e1002228
    [Google Scholar]
  183. 183.  Tang A, Huang Y, Li Z, Wan S, Mou L et al. 2016. Analysis of a four generation family reveals the widespread sequence-dependent maintenance of allelic DNA methylation in somatic and germ cells. Sci. Rep. 6:19260
    [Google Scholar]
  184. 184.  Whitelaw E 2015. Sperm DNA methylation: Not a vehicle for dietary reprogramming of offspring?. Dev. Cell 35:668–69
    [Google Scholar]
  185. 185.  Aarabi M, San Gabriel MC, Chan D, Behan NA, Caron M et al. 2015. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum. Mol. Genet. 24:6301–13
    [Google Scholar]
  186. 186.  Aiken CE, Ozanne SE 2013. Sex differences in developmental programming models. Reproduction 145:R1–13
    [Google Scholar]
  187. 187.  Steele W, Allegrucci C, Singh R, Lucas E, Priddle H et al. 2005. Human embryonic stem cell methyl cycle enzyme expression: Modelling epigenetic programming in assisted reproduction?. Reprod. Biomed. Online 10:755–66
    [Google Scholar]
  188. 188.  Sunde A, Brison D, Dumoulin J, Harper J, Lundin K et al. 2016. Time to take human embryo culture seriously. Hum. Reprod. 31:2174–82
    [Google Scholar]
  189. 189.  Calhaz-Jorge C, De Geyter C, Kupka MS, de Mouzon J, Erb K et al. 2017. Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum. Reprod. 32:1957–73
    [Google Scholar]
  190. 190.  Berntsen S, Pinborg A 2018. Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART). Birth Defects Res 110:630–43
    [Google Scholar]
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