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From Genetics to Epigenetics: New Insights into Male Reproduction

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Pediatric and Adolescent Andrology

Part of the book series: Trends in Andrology and Sexual Medicine ((TASM))

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Abstract

Epigenetic regulation plays an important role in human reproduction. In this section, we will focus on the most recent discoveries in the field of epigenetics of male fertility. We will describe the effects of epigenetic modifications, responsive to environmental agents and lifestyle factors, on spermatogenesis failure, embryonic development, outcome of assisted reproduction technique (ART) protocols, and the offspring phenotype during lifetime. Since epigenetic modifications are reversible, recent findings suggest the sperm epigenome as a potential diagnostic tool and therapeutic target in the management of male reproduction health. In particular, specific attention to the personal lifestyle care, including personalized nutrition, could prevent or reverse detrimental epigenetic modifications induced by environmental and lifestyle stressors.

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References

  1. Geelhoed DW, Nayembil D, Asare K, Schagen van Leeuwen JH, van Roosmalen J. Infertility in rural Ghana. Int J Gynaecol Obstet. 2002;79(2):137–42. https://doi.org/10.1016/S0020-7292(02)00237-0.

    Article  CAS  PubMed  Google Scholar 

  2. Klemetti R, Raitanen J, Sihvo S, Saarni S, Koponen P. Infertility, mental disorders and well-being—a nationwide survey. Acta Obstet Gynecol Scand. 2010;89(5):677–82. https://doi.org/10.3109/00016341003623746.

    Article  PubMed  Google Scholar 

  3. Louis JF, Thoma ME, Sørensen DN, McLain AC, King RB, Sundaram R, Keiding N, Buck Louis GM. The prevalence of couple infertility in the United States from a male perspective: evidence from a nationally representative sample. Andrology. 2013;1:741–8. https://doi.org/10.1111/j.2047-2927.2013.00110.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Datta J, Palmer MJ, Tanton C, Gibson LJ, Jones KG, Macdowall W, Glasier A, Sonnenberg P, Field N, Mercer CH, et al. Prevalence of infertility and help seeking among 15000 women and men. Hum Reprod. 2016;31:2108–18. https://doi.org/10.1093/humrep/dew123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Katz DJ, Teloken P, Shoshany O. Male infertility - The other side of the equation. Aust Fam Physician. 2017;46(9):641–6.

    PubMed  Google Scholar 

  6. Stuppia L, Gatta V, Antonucci I, Giuliani R, Scioletti AP, Palka G. Genetic testing in couples undergoing assisted reproduction technique protocols. Expert Opin Med Diagn. 2009;3(5):571–83. https://doi.org/10.1517/17530050902970986. Epub 2009 Jul 29.

    Article  CAS  PubMed  Google Scholar 

  7. Thirumavalavan N, Gabrielsen JS, Lamb DJ. Where are we going with gene screening for male infertility? Fertil Steril. 2019;111(5):842–50. https://doi.org/10.1016/j.fertnstert.2019.03.036. Review.

    Article  PubMed  Google Scholar 

  8. Fenz Araujo T, Friedrich C, Paiva Grangeiro CH, Martelli LR, Emich J, Wyrwoll MJ, Kliesch S, Simões AL, Tüttelmann F. Sequence analysis of 37 candidate genes for male infertility: challenges in variant assessment and validating genes. Andrology. 2019; https://doi.org/10.1111/andr.12704.

  9. Tüttelmann F, Ruckert C, Röpke A. Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20 years of unchanged routine. Med Genet. 2018;30(1):12–20. https://doi.org/10.1007/s11825-018-0181-7. Epub 2018 Feb 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Waddington CH. The epigenotype. Endeavour. 1942;1:18–20. https://doi.org/10.1093/ije/dyr184. Epub 2011 Dec 20.

    Article  Google Scholar 

  11. Riggs AD, Matienssen RA, Russo VEA. Introduction. In: Epigenetic mechanisms of gene regulation. Cold Spring Harbour, NY: Cold Spring Harbour Laboratory Press; 1996. p. 1–4.

    Google Scholar 

  12. Holliday R. Epigenetics: a historical overview. Epigenetics. 2006;1:76–80. https://doi.org/10.4161/epi.1.2.2762.

    Article  PubMed  Google Scholar 

  13. Uysal F, Akkoyunlu G, Ozturk S. DNA methyltransferases exhibit dynamic expression during spermatogenesis. Reprod Biomed Online. 2016;33:690–702. https://doi.org/10.1016/j.rbmo.2016.08.022.

    Article  CAS  PubMed  Google Scholar 

  14. Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013;502(7472):472–9. https://doi.org/10.1038/nature12750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Patil V, Ward RL, Hesson LB. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics. 2014;9(6):823–8. https://doi.org/10.4161/epi.28741. Epub 2014 Apr 9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705. https://doi.org/10.1016/j.cell.2007.02.005.

    Article  CAS  Google Scholar 

  17. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–5. https://doi.org/10.1038/47412.

    Article  CAS  PubMed  Google Scholar 

  18. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074–80.

    Article  CAS  Google Scholar 

  19. Dadoune JP. Spermatozoal RNAs: what about their functions? Microsc Res Tech. 2009;72:536–51. https://doi.org/10.1002/jemt.20697.

    Article  CAS  PubMed  Google Scholar 

  20. Wei JW, Huang K, Yang C, Kang CS. Non-coding RNAs as regulators in epigenetics (review). Oncol Rep. 2017;37(1):3–9. https://doi.org/10.3892/or.2016.5236. Epub 2016 Nov 8.

    Article  PubMed  Google Scholar 

  21. Butler MG. Genomic imprinting disorders in humans: a mini-review. J Assist Reprod Genet. 2009;26:477–86. https://doi.org/10.1007/s10815-009-9353-3.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Neto FT, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol. 2016;59:10–26. https://doi.org/10.1016/j.semcdb.2016.04.009. Epub 2016 Apr 30.

    Article  PubMed  Google Scholar 

  23. Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R. Chromatin dynamics during spermiogenesis. Biochim Biophys Acta. 1839;2014:155–68. https://doi.org/10.1016/j.bbagrm.2013.08.004.

    Article  CAS  Google Scholar 

  24. Sonnack V, Failing K, Bergmann M, Steger K. Expression of hyperacetylated histone H4 during normal and impaired human spermatogenesis. Andrologia. 2002;34:384–90. https://doi.org/10.1046/j.1439-0272.2002.00524.x.

    Article  CAS  PubMed  Google Scholar 

  25. Meistrich ML, Mohapatra B, Shirley CR, Zhao M. Roles of transition nuclear proteins in spermiogenesis. Chromosoma. 2003;111:483–8.

    Article  Google Scholar 

  26. Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001;22:604–10. https://doi.org/10.1002/j.1939-4640.2001.tb02220.x.

    Article  CAS  PubMed  Google Scholar 

  27. de Mateo S, Gázquez C, Guimerà M, Balasch J, Meistrich ML, Ballescà JL, Oliva R. Protamine 2 precursors (Pre–P2), protamine 1 to protamine 2 ratio (P1/P2), and assisted reproduction outcome. Fertil Steril. 2009;91:715–22. https://doi.org/10.1016/j.fertnstert.2007.12.047.

    Article  CAS  PubMed  Google Scholar 

  28. Carrell DT. Epigenetics of the male gamete. Fertil Steril. 2012;97:267–74. https://doi.org/10.1016/j.fertnstert.2011.12.036.

    Article  CAS  PubMed  Google Scholar 

  29. Ge SQ, Li SL, Zhao ZH, Sun QY. Epigenetic dynamics and interplay during spermatogenesis and embryogenesis: implications for male fertility and offspring health. Oncotarget. 2017;8(32):53,804–18. https://doi.org/10.18632/oncotarget.17479.

    Article  Google Scholar 

  30. Boissonnas CC, Jouannet P, Jammes H. Epigenetic disorders and male subfertility. Fertil Steril. 2013;99:624–31. https://doi.org/10.1016/j.fertnstert.2013.01.124.

    Article  CAS  PubMed  Google Scholar 

  31. Sharma U, Sun F, Conine CC, Reichholf B, Kukreja S, Herzog VA, Ameres SL, Rando OJ. Small RNAs are trafficked from the epididymis to developing mammalian sperm. Dev Cell. 2018;46(4):481–494.e6. https://doi.org/10.1016/j.devcel.2018.06.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Reilly JN, McLaughlin EA, Stanger SJ, Anderson AL, Hutcheon K, Church K, Mihalas BP, Tyagi S, Holt JE, Eamens AL, Nixon B. Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. Sci Rep. 2016;6:31794. https://doi.org/10.1038/srep31794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460:473–8. https://doi.org/10.1038/nature08162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Stuppia L, Franzago M, Ballerini P, Gatta V, Antonucci I. Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clin Epigenetics. 2015;7:120. https://doi.org/10.1186/s13148-015-0155-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sallmén M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology. 2006;17(5):520–3. https://doi.org/10.1097/01.ede.0000229953.76862.e5.

    Article  PubMed  Google Scholar 

  36. Nguyen RH, Wilcox AJ, Skjærven R, Baird DD. Men’s body mass index and infertility. Hum Reprod. 2007;22(9):2488–93. https://doi.org/10.1093/humrep/dem139.

    Article  PubMed  Google Scholar 

  37. Ramlau-Hansen CH, Thulstrup AM, Aggerholm AS, Jensen MS, Toft G, Bonde JP. Is smoking a risk factor for decreased semen quality? A cross-sectional analysis. Hum Reprod. 2007;22(1):188–96. https://doi.org/10.1093/humrep/del364.

    Article  CAS  PubMed  Google Scholar 

  38. Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sørensen TIA, Olsen J. Subfecundity in overweight and obese couples. Hum Reprod. 2007;22(6):1634–7. https://doi.org/10.1093/humrep/dem035.

    Article  CAS  PubMed  Google Scholar 

  39. Steegers-Theunissen RPM, Twigt J, Pestinger V, Sinclair KD. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update. 2013;19:640–55. https://doi.org/10.1093/humupd/dmt041.

    Article  CAS  PubMed  Google Scholar 

  40. Alegría-Torres JA, Baccarelli A, Bollati V. Epigenetics and lifestyle. Epigenomics. 2011;3:267–77. https://doi.org/10.2217/epi.11.22.

    Article  CAS  PubMed  Google Scholar 

  41. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. 2013;11:66. https://doi.org/10.1186/1477-7827-11-66.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Soubry A, Guo L, Huang Z, Hoyo C, Romanus S, Price T, Murphy SK. Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics. 2016;8:51. https://doi.org/10.1186/s13148-016-0217-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sermondade N, Faure C, Fezeu L, Lévy R, Czernichow S. Obesity and increased risk for oligozoospermia and azoospermia. Arch Intern Med. 2012;172(5):440–2. https://doi.org/10.1001/archinternmed.2011.1382.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update. 2013;19(3):221–31. https://doi.org/10.1093/humupd/dms050.

    Article  CAS  PubMed  Google Scholar 

  45. Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, Mortensen B, et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 2016;23(2):369–78. https://doi.org/10.1016/j.cmet.2015.11.004.

    Article  CAS  PubMed  Google Scholar 

  46. Gaur DS, Talekar MS, Pathak VP. Alcohol intake and cigarette smoking: impact of two major lifestyle factors on male fertility. Indian J Pathol Microbiol. 2010;53(1):35. https://doi.org/10.4103/0377-4929.59180.

    Article  PubMed  Google Scholar 

  47. Jensen TK, Swan S, Jørgensen N, Toppari J, Redmon B, et al. Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA. Hum Reprod. 2014;29:1801–9. https://doi.org/10.1093/humrep/deu118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ouko LA, Shantikumar K, Knezovich J, Haycock P, Schnugh DJ, Ramsay M. Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes: implications for fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2009;33:1615–27. https://doi.org/10.1111/j.1530-0277.2009.00993.x.

    Article  CAS  PubMed  Google Scholar 

  49. Tunc O, Tremellen K. Oxidative DNA damage impairs global sperm DNA 21 methylation in infertile men. J Assist Reprod Genet. 2009;26:537–44. https://doi.org/10.1007/s10815-009-9346-2.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018;4(2):dvy007. https://doi.org/10.1093/eep/dvy007. eCollection 2018 Apr.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sharma R, Harlev A, Agarwal A, Esteves SC. Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010 World Health Organization laboratory methods for the examination of human semen. Eur Urol. 2016;70(4):635–45. https://doi.org/10.1016/j.eururo.2016.04.010.

    Article  PubMed  Google Scholar 

  52. Jenkins TG, James ER, Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, Cairns BR, Carrell DT, Aston KI. Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology. 2017;5(6):1089–99. https://doi.org/10.1111/andr.12416. Epub 2017 Sep 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Marczylo EL, Amoako AA, Konje JC, Gant TW, Marczylo TH. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics. 2012;7:432–9. https://doi.org/10.4161/epi.19794.

    Article  CAS  PubMed  Google Scholar 

  54. Denham J, O’Brien BJ, Harvey JT, Charchar FJ. Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics. 2015;7(5):717–31. https://doi.org/10.2217/epi.15.29. Epub 2015 Apr 13.

    Article  CAS  PubMed  Google Scholar 

  55. Ingerslev LR, Donkin I, Fabre O, Versteyhe S, Mechta M, et al. Endurance training remodels sperm-borne small RNA expression and methylation at neurological gene hotspots. Clin Epigenetics. 2018;10:12. https://doi.org/10.1186/s13148-018-0446-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Franzago M, La Rovere M, Guanciali Franchi P, Vitacolonna E, Stuppia L. Epigenetics and human reproduction: the primary prevention of the non-communicable diseases. Epigenomics. 2019; https://doi.org/10.2217/epi-2019-0163.

  57. Chao SB, Chen L, Li JC, Ou XH, Huang XJ, Wen S, Sun QY, Gao GL. Defective histone H3K27 trimethylation modification in embryos derived from heated mouse sperm. Microsc microanal. 2012;18:476–82. https://doi.org/10.1017/S1431927612000396.

    Article  CAS  PubMed  Google Scholar 

  58. Rahman MB, Kamal MM, Rijsselaere T, Vandaele L, Shamsuddin M, Van Soom A. Altered chromatin condensation of heat-stressed spermatozoa perturbs the dynamics of DNA methylation reprogramming in the paternal genome after in vitro fertilisation in cattle. Reprod Fertil Dev. 2014;26(8):1107–16. https://doi.org/10.1071/RD13218.

    Article  CAS  PubMed  Google Scholar 

  59. Tavalaee M, Bahreinian M, Barekat F, Abbasi H, Nasr-Esfahani MH. Effect of varicocelectomy on sperm functional characteristics and DNA methylation. Andrologia. 2015;47(8):904–9. https://doi.org/10.1111/and.12345.

    Article  CAS  PubMed  Google Scholar 

  60. Garolla A, Torino M, Miola P, Caretta N, Pizzol D, Menegazzo M, Bertoldo A, Foresta C. Twenty-four hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function. Hum Reprod. 2015;30(5):1006–13. https://doi.org/10.1093/humrep/dev057. Epub 2015 Mar 15.

    Article  CAS  PubMed  Google Scholar 

  61. Garolla A, Torino M, Sartini B, Cosci I, Patassini C, Carraro U, Foresta C. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013;28(4):877–85. https://doi.org/10.1093/humrep/det020. Epub 2013 Feb 14.

    Article  CAS  PubMed  Google Scholar 

  62. Bhongade MB, Prasad S, Jiloha RC, Ray PC, Mohapatra S, Koner BC. Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples. Andrologia. 2015;47(3):336–42. https://doi.org/10.1111/and.12268. Epub 2014 Mar 26.

    Article  CAS  PubMed  Google Scholar 

  63. Dickson DA, Paulus JK, Mensah V, Lem J, Saavedra-Rodriguez L, Gentry A, Pagidas K, Feig LA. Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress. Transl Psychiatry. 2018;8(1):101. https://doi.org/10.1038/s41398-018-0146-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pang TYC, Short AK, Bredy TW, Hannan AJ. Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes. Curr Opin Behav Sci. 2017;14:140–7. https://doi.org/10.1016/j.cobeha.2017.02.007. Epub 2017 Mar 8.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hur SSJ, Cropley JE, Suter CM. Paternal epigenetic programming: evolving metabolic disease risk. J Mol Endocrinol. 2017;58(3):R159–68. https://doi.org/10.1530/JME-16-0236. Epub 2017 Jan 18.

    Article  CAS  PubMed  Google Scholar 

  66. Rowold ED, Schulze L, Van der Auwera S, Grabe HJ. Paternal transmission of early life traumatization through epigenetics: do fathers play a role? Med Hypotheses. 2017;109:59–64. https://doi.org/10.1016/j.mehy.2017.09.011. Epub 2017 Sep 18.

    Article  PubMed  Google Scholar 

  67. Romerius P, Ståhl O, Moëll C, Relander T, Cavallin-Ståhl E, Gustafsson H, Löfvander Thapper K, Jepson K, Spanò M, Wiebe T, Lundberg Giwercman Y, Giwercman A. Sperm DNA integrity in men treated for childhood cancer. Clin Cancer Res. 2010;16(15):3843–50. https://doi.org/10.1158/1078-0432.CCR-10-0140.

    Article  PubMed  Google Scholar 

  68. Fischbein A, Zabludovsky N, Eltes F, Grischenko V, Bartoov B. Ultramorphological sperm characteristics in the risk assessment of health effects after radiation exposure among salvage workers in Chernobyl. Environ Health Perspect. 1997;105:1445–9. https://doi.org/10.1289/ehp.97105s61445.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zhou DD, Hao JL, Guo KM, Lu CW, Liu XD. Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation. Genet Mol Res. 2016 Mar;22:15(1). https://doi.org/10.4238/gmr.15018078.

    Article  CAS  Google Scholar 

  70. Kumar D, Salian SR, Kalthur G, Uppangala S, Kumari S, Challapalli S, Chandraguthi SG, Krishnamurthy H, Jain N, Kumar P, Adiga SK. Semen abnormalities, sperm DNA damage and global hypermethylation in health workers occupationally exposed to ionizing radiation. PLoS One. 2013;8(7):e69927. https://doi.org/10.1371/journal.pone.0069927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21(2):243–51.

    Article  Google Scholar 

  72. Jeng HA, Yu L. Alteration of sperm quality and hormone levels by polycyclic aromatic hydrocarbons on airborne particulate particles. J Environ Sci Health A. 2008;43(7):675–81.

    Article  CAS  Google Scholar 

  73. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-Jones K, Peterson CM. Decreased sperm motility is associated with air pollution in salt Lake City. Fertil Steril. 2010;93:1875–9.

    Article  Google Scholar 

  74. Hammoud SS, Purwar J, Pflueger C, Cairns BR, Carrell DT. Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril. 2010;94:1728–33.

    Article  CAS  Google Scholar 

  75. Anawalt BD. The silent spermatozoon: are man-made endocrine disruptors killing male fertility? Asian J Androl. 2013;15:165–8. https://doi.org/10.1038/aja.2012.148.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Sifakis S, Androutsopoulos VP, Tsatsakis AM, Spandidos DA. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems. Environ Toxicol Pharmacol. 2017;51:56–70. https://doi.org/10.1016/j.etap.2017.02.024. Epub 2017 Mar 6.

    Article  CAS  PubMed  Google Scholar 

  77. Lassen TH, Frederiksen H, Jensen TK, Petersen JH, Joensen UN, Main KM, et al. Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality. Environ Health Perspect. 2014;122:478–84. https://doi.org/10.1289/ehp.1307309.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Zheng H, Zhou X, Li DK, Yang F, Pan H, Li T, Miao M, Li R, Yuan W. Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men. PLoS One. 2017;12:e0178535. https://doi.org/10.1371/journal.pone.0178535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Schrader SM, Turner TW, Ratcliffe JM. The effects of ethylene dibromide on semen quality: a comparison of short-term and chronic exposure. Reprod Toxicol (Elmsford, NY). 1988;2:191–8.

    Article  CAS  Google Scholar 

  80. Bretveld R, Brouwers M, Ebisch I, Roeleveld N. Influence of pesticides on male fertility. Scand J Work Environ Health. 2007;33(1):13–28.

    Article  CAS  Google Scholar 

  81. Amir D. The spermicidal effect of ethylene dibromide in bulls and rams. Mol Reprod Dev. 1991;28:99–109. https://doi.org/10.1002/mrd.1080280116.

    Article  CAS  PubMed  Google Scholar 

  82. Selevan SG, Borkovec L, Slott VL, Zudova Z, Rubes J, Evenson DP, Perreault SD. Semen quality and reproductive health of young Czech men exposed to seasonal air pollution. Environ Health Perspect. 2010;108:887–94. https://doi.org/10.1289/ehp.00108887.

    Article  Google Scholar 

  83. Rubes J, Rybar R, Prinosilova P, Veznik Z, Chvatalova I, Solansky I, Sram RJ. Genetic polymorphisms influence the susceptibility of men to sperm DNA damage associated with exposure to air pollution. Mutat Res. 2010;683:9–15. https://doi.org/10.1016/j.mrfmmm.2009.09.010.

    Article  CAS  PubMed  Google Scholar 

  84. Radwan M, Jurewicz J, Polańska K, Sobala W, Radwan P, Bochenek M, Hanke W. Exposure to ambient air pollution—does it affect semen quality and the level of reproductive hormones? Ann Hum Biol. 2016;43:50–6.

    Article  Google Scholar 

  85. Vecoli C, Montano L, Andreassi MG. Environmental pollutants: genetic damage and epigenetic changes in male germ cells. Environ Sci Pollut Res Int. 2016;23(23):23,339–48. Epub 2016 Sep 26. https://doi.org/10.1007/s11356-016-7728-4.

    Article  CAS  Google Scholar 

  86. Yauk C, Polyzos A, Rowan-Carroll A, Somers CM, Godschalk RW, Van Schooten FJ, Berndt ML, Pogribny IP, Koturbash I, Williams A, et al. Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proc Natl Acad Sci U S A. 2008;105:605–10.

    Article  CAS  Google Scholar 

  87. Tollefsbol TO. Generational epigenetic inheritance. In: Tollefsbol TO, editor. Transgenerational epigenetics. Cambridge, MA: Academic Press; 2019. p. 1–10.

    Google Scholar 

  88. Canovas S, Ross PJ, Kelsey G. Coy PDNA methylation in embryo development: epigenetic impact of ART (assisted reproductive technologies). BioEssays. 2017;39 https://doi.org/10.1002/bies.201700106.

  89. Bowman P, McLaren A. Viability and growth of mouse embryos after in vitro culture and fusion. J Embryol Exp Morphol. 1970;23:693–704.

    CAS  PubMed  Google Scholar 

  90. Roemer I, Reik W, Dean W, Klose J. Epigenetic inheritance in the mouse. Curr Biol. 1997;7:277–80.

    Article  CAS  Google Scholar 

  91. Dean W, Bowden L, Aitchison A, Klose J, Moore T, Meneses JJ, Reik W, Feil R. Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes. Development. 1998;125:2273–82.

    Article  CAS  Google Scholar 

  92. Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod. 2000;62:1526–35.

    Article  CAS  Google Scholar 

  93. Khosla S, Dean W, Brown D, Reik W, Feil R. Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod. 2001;64:918–26.

    Article  CAS  Google Scholar 

  94. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet. 2001;27:153–4.

    Article  CAS  Google Scholar 

  95. Young LE, Schnieke AE, McCreath KJ, Wieckowski S, Konfortova G, Fernandes K, Ptak G, Kind AJ, Wilmut I, Loi P, et al. Conservation of IGF2-H19 and IGF2R imprinting in sheep: effects of somatic cell nuclear transfer. Mech Dev. 2003;120:1433–42.

    Article  CAS  Google Scholar 

  96. Young LE, Sinclair KD, Wilmut I. Large offspring syndrome in cattle and sheep. Rev Reprod. 1998;3:155–63.

    Article  CAS  Google Scholar 

  97. Filipponi D, Feil R. Perturbation of genomic imprinting in oligozoospermia. Epigenetics. 2009;4:27–30.

    Article  CAS  Google Scholar 

  98. Kobayashi H, Hiura H, John RM, Sato A, Otsu E, Kobayashi N, Suzuki R, et al. DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm. Eur J Hum Genet. 2009;17:1582–91. https://doi.org/10.1038/ejhg.2009.68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Liu H, Zhang Y, Gu HT, Feng QL, Liu JY, Zhou J, Yan F. Association between assisted reproductive technology and cardiac alteration at age 5 years. JAMA Pediatr. 2015;169:603–5. https://doi.org/10.1001/jamapediatrics.2015.0214.

    Article  PubMed  Google Scholar 

  100. Guo XY, Liu XM, Jin L, Wang TT, Ullah K, Sheng JZ, Huang HF. Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertil Steril. 2017;107:622–31. https://doi.org/10.1016/j.fertnstert.2016.12.007.

    Article  PubMed  Google Scholar 

  101. Kosteria I, Tsangaris GT, Gkourogianni A, Anagnostopoulos A, Papadopoulou A, Papassotiriou I, Loutradis D, Chrousos GP, Kanaka-Gantenbein C. Proteomics of children born after intracytoplasmic sperm injection reveal indices of an adverse cardiometabolic profile. J Endocr Soc. 2017;1:288–301. https://doi.org/10.1210/js.2016-1052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. La Rovere M, Franzago M, Stuppia L. Epigenetics and Neurological Disorders in ART. Int J Mol Sci. 2019; 20(17). pii: E4169. https://doi.org/10.3390/ijms20174169. Review.

  103. Whitelaw N, Bhattacharya S, Hoad G, Horgan GW, Hamilton M, Haggarty P. Epigenetic status in the offspring of spontaneous and assisted conception. Hum Reprod. 2014;29:1452–8.

    Article  CAS  Google Scholar 

  104. Chen M, Heilbronn LK. The health outcomes of human offspring conceived by assisted reproductive technologies (ART). J Dev Orig Health Dis. 2017;8:388–402. https://doi.org/10.1017/S2040174417000228.

    Article  CAS  PubMed  Google Scholar 

  105. Szarc vel Szic K, Declerck K, Vidaković M, Vanden Berghe W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin Epigenetics. 2015;7:33. https://doi.org/10.1186/s13148-015-0068-2. eCollection 2015.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine and Aging, School of Medicine and Health Sciences, “G. d’Annunzio” University, Chieti-Pescara, Italy

    Marica Franzago

  2. Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University, Chieti-Pescara, Italy

    Marica Franzago & Liborio Stuppia

  3. Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University, Chieti-Pescara, Italy

    Liborio Stuppia

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  1. Marica Franzago
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  2. Liborio Stuppia
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Correspondence to Liborio Stuppia .

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Editors and Affiliations

  1. Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padua, Padova, Italy

    Carlo Foresta

  2. Department of Experimental Medicine, Section of Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Roma, Italy

    Daniele Gianfrilli

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Franzago, M., Stuppia, L. (2021). From Genetics to Epigenetics: New Insights into Male Reproduction. In: Foresta, C., Gianfrilli, D. (eds) Pediatric and Adolescent Andrology. Trends in Andrology and Sexual Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-80015-4_3

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