Epigenetic Transgenerational Inheritance

  • Joan Blanco RodríguezEmail author
  • Cristina Camprubí Sánchez
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1166)


Epigenetic information refers to heritable changes in gene expression that occur without modifications at the DNA sequence level. These changes are orchestrated by different epigenetic mechanisms such as DNA methylation, posttranslational modifications of histones, and the presence of noncoding RNAs. Epigenetic information regulates chromatin structure to confer cell-specific gene expression.

The sperm epigenome is the result of three periods of global resetting during men’s life. Germ cell epigenome reprogramming is designed to allow cell totipotency and to prevent the transmission of epimutations via spermatozoa. At the end of these reprogramming events, the sperm epigenome has a very specific epigenetic pattern that is a footprint of past reprogramming events and has an influence on embryo development.

Several data demonstrate that not all regions of the epigenome are erased during the reprogramming periods, suggesting the transmission of epigenetic information from fathers to offspring via spermatozoa. Moreover, it is becoming increasingly clear that the sperm epigenome is sensitive to environmental factors during the process of gamete differentiation, suggesting the plasticity of the sperm epigenetic signature according to the circumstances of the individual’s life.

In this chapter, we provided strong evidences about the association between variations of the sperm epigenome and the exposure to environmental factors. Moreover, we will present data about how epigenetic mechanisms are candidates for transferring paternal environmental information to offspring.


Spermatozoa Epigenome Chromatin Transgenerational inheritance DNA methylation Noncoding RNA 


  1. Aarabi M, San Gabriel MC, Chan D, Behan NA, Caron M, Pastinen T, Bourque G, MacFarlane AJ, Zini A, Trasler J (2015) High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet 24:6301–6313PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aboulmaouahib S, Madkour A, Kaarouch I, Sefrioui O, Saadani B, Copin H, Benkhalifa M, Louanjli N, Cadi R (2018) Impact of alcohol and cigarette smoking consumption in male fertility potential: looks at lipid peroxidation, enzymatic antioxidant activities and sperm DNA damage. Andrologia 50:e12926CrossRefGoogle Scholar
  3. Al Khaled Y, Tierling S, Laqqan M, Lo Porto C, Hammadeh ME (2018) Cigarette smoking induces only marginal changes in sperm DNA methylation levels of patients undergoing intracytoplasmic sperm injection treatment. Andrologia 50:e12818CrossRefGoogle Scholar
  4. Amanai M, Brahmajosyula M, Perry ACF (2006) A restricted role for sperm-borne MicroRNAs in mammalian fertilization. Biol Reprod 75:877–884PubMedCrossRefGoogle Scholar
  5. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469PubMedCrossRefGoogle Scholar
  6. Arpanahi A, Brinkworth M, Iles D, Krawetz SA, Paradowska A, Platts AE, Saida M, Steger K, Tedder P, Miller D (2009) Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res 19:1338–1349PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bahreinian M, Tavalaee M, Abbasi H, Kiani-Esfahani A, Shiravi AH, Nasr-Esfahani MH (2015) DNA hypomethylation predisposes sperm to DNA damage in individuals with varicocele. Syst Biol Reprod Med 61:179–186PubMedCrossRefGoogle Scholar
  8. Bao J, Wu J, Schuster AS, Hennig GW, Yan W (2013) Expression profiling reveals developmentally regulated lncRNA repertoire in the mouse male germline. Biol Reprod 89:107PubMedPubMedCentralCrossRefGoogle Scholar
  9. Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, Guérin JF (2005) Influence of global sperm DNA methylation on IVF results. Hum Reprod 20:768–773PubMedCrossRefGoogle Scholar
  10. Bielawski DM, Zaher FM, Svinarich DM, Abel EL (2002) Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels. Alcohol Clin Exp Res 26:347–351PubMedCrossRefPubMedCentralGoogle Scholar
  11. Boerke A, Dieleman SJ, Gadella BM (2007) A possible role for sperm RNA in early embryo development. Theriogenology 68(Suppl 1):S147–S155PubMedCrossRefPubMedCentralGoogle Scholar
  12. Borgel J, Guibert S, Li Y, Chiba H, Schübeler D, Sasaki H, Forné T, Weber M (2010) Targets and dynamics of promoter DNA methylation during early mouse development. Nat Genet 42:1093–1100PubMedCrossRefPubMedCentralGoogle Scholar
  13. Branco MR, Oda M, Reik W (2008) Safeguarding parental identity: Dnmt1 maintains imprints during epigenetic reprogramming in early embryogenesis. Genes Dev 22:1567–1571PubMedPubMedCentralCrossRefGoogle Scholar
  14. Brunner AM, Nanni P, Mansuy IM (2014) Epigenetic marking of sperm by post-translational modification of histones and protamines. Epigenetics Chromatin 7(2)Google Scholar
  15. Camprubí C, Salas-Huetos A, Aiese-Cigliano R, Godo A, Pons MC, Castellano G, Grossmann M, Sanseverino W, Martin-Subero JI, Garrido N, Blanco J (2016) Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis. Reprod Biomed Online 33:709–719PubMedCrossRefPubMedCentralGoogle Scholar
  16. Camprubí C, Aiese-Cigliano R, Salas-Huetos A, Garrido N, Blanco J (2017) What the human sperm methylome tells us. Epigenomics 9:1299–1315PubMedCrossRefPubMedCentralGoogle Scholar
  17. Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–1096PubMedPubMedCentralCrossRefGoogle Scholar
  18. Chan D, Delbe’s G, Landry M, Robaire B, Trasler JM (2012) Epigenetic alterations in sperm DNA associated with testicular cancer treatment. Toxicol Sci 125:532–543CrossRefGoogle Scholar
  19. Chu MW, Siegmund KD, Eckstam CL, Kim JY, Yang AS, Kanel GC, Tavaré S, Shibata D (2007) Lack of increases in methylation at three CpG-rich genomic loci in non-mitotic adult tissues during aging. BMC Med Genet 8:50PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chuma S, Nakano T (2012) piRNA and spermatogenesis in mice. Philos Trans R Soc London B Biol Sci 368:20110338CrossRefGoogle Scholar
  21. Chuva de Sousa Lopes SM, Roelen BAJ (2010) On the formation of germ cells: the good, the bad and the ugly. Differentiation 79:131–140PubMedCrossRefPubMedCentralGoogle Scholar
  22. Consales C, Toft G, Leter G, Bonde JPE, Uccelli R, Pacchierotti F, Eleuteri P, Jönsson BAG, Giwercman A, Pedersen HS, Struciński P, Góralczyk K, Zviezdai V, Spanò M (2016) Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations. Environ Mol Mutagen 57:200–209PubMedCrossRefPubMedCentralGoogle Scholar
  23. Corral-Vazquez C, Anton E (2018) Epigenetic and assisted reproduction experimental studies: sperm ncRNAs. In: Blanco J, Camprubí C (eds) Epigenetics and assisted reproduction an introductory guide. Taylor & Francis, Boca RatonGoogle Scholar
  24. Davis TL, Yang GJ, McCarrey JR, Bartolomei MS (2000) The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Hum Mol Genet 9:2885–2894PubMedCrossRefPubMedCentralGoogle Scholar
  25. de Castro Barbosa T, Ingerslev LR, Alm PS, Versteyhe S, Massart J, Rasmussen M, Donkin I, Sjögren R, Mudry JM, Vetterli L, Gupta S, Krook A, Zierath JR, Barrès R (2016) High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Mol Metab 5:184–197PubMedCrossRefPubMedCentralGoogle Scholar
  26. de Mateo S, Sassone-Corsi P (2014) Regulation of spermatogenesis by small non-coding RNAs: role of the germ granule. Semin Cell Dev Biol 29:84–92PubMedPubMedCentralCrossRefGoogle Scholar
  27. Denham J, O’Brien BJ, Harvey JT, Charchar FJ (2015) Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7:1–15CrossRefGoogle Scholar
  28. Denomme MM, McCallie BR, Parks JC, Schoolcraft WB, Katz-Jaffe MG (2017) Alterations in the sperm histone-retained epigenome are associated with unexplained male factor infertility and poor blastocyst development in donor oocyte IVF cycles. Hum Reprod 32:1–13CrossRefGoogle Scholar
  29. Ding GL, Wang FF, Shu J, Tian S, Jiang Y, Zhang D, Wang N, Luo Q, Zhang Y, Jin F, Leung PCK, Sheng JZ, Huang HF (2012) Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes 61:1133–1142PubMedPubMedCentralCrossRefGoogle Scholar
  30. Ding G-L, Liu Y, Liu M-E, Pan J-X, Guo M-X, Sheng J-Z, Huang H-F (2015) The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian J Androl 17:948PubMedPubMedCentralCrossRefGoogle Scholar
  31. Doerksen T, Trasler JM (1996) Developmental exposure of male germ cells to 5-Azacytidine results in abnormal preimplantation development in rats. Biol Reprod 55:1155–1162PubMedCrossRefGoogle Scholar
  32. Doerksen T, Benoit G, Trasler JM (2000) Deoxyribonucleic acid hypomethylation of male germ cells by mitotic and meiotic exposure to 5-azacytidine is associated with altered testicular histology. Endocrinology 141:3235–3244PubMedCrossRefGoogle Scholar
  33. Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, Mortensen B, Appel EVR, Jørgensen N, Kristiansen VB, Hansen T, Workman CT, Zierath JR, Barrès R (2016) Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab 23:369–378PubMedCrossRefGoogle Scholar
  34. Du Plessis SS, Cabler S, McAlister DA, Sabanegh E, Agarwal A (2010) The effect of obesity on sperm disorders and male infertility. Nat Rev Urol 7:153–161PubMedCrossRefGoogle Scholar
  35. Eisenberg ML, Meldrum D (2017) Effects of age on fertility and sexual function. Fertil Steril 107:301–304PubMedCrossRefGoogle Scholar
  36. Ellegaard PK, Poulsen HE (2016) Tobacco smoking and oxidative stress to DNA: a meta-analysis of studies using chromatographic and immunological methods. Scand J Clin Lab Invest 76:151–158PubMedCrossRefGoogle Scholar
  37. Finegersh A, Homanics GE (2014) Paternal alcohol exposure reduces alcohol drinking and increases behavioral sensitivity to alcohol selectively in male offspring. PLoS One 9:e99078PubMedPubMedCentralCrossRefGoogle Scholar
  38. Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI (2008) Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett 266:6–11PubMedCrossRefGoogle Scholar
  39. Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, Print CG, Owens JA, Lane M (2013) Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J 27:4226–4243PubMedCrossRefGoogle Scholar
  40. Fullston T, Ohlsson-Teague EMC, Print CG, Sandeman LY, Lane M (2016) Sperm microRNA content is altered in a mouse model of male obesity, but the same suite of microRNAs are not altered in offspring’s sperm. PLoS One 11:e0166076PubMedPubMedCentralCrossRefGoogle Scholar
  41. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17:667–669PubMedPubMedCentralCrossRefGoogle Scholar
  42. Garro AJ, McBeth DL, Lima V, Lieber CS (1991) Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res 15:395–398PubMedCrossRefGoogle Scholar
  43. Gatewood JM, Cook GR, Balhorn R, Bradbury EM, Schmid CW (1987) Sequence-specific packaging of DNA in human sperm chromatin. Science 236:962–964PubMedCrossRefGoogle Scholar
  44. Ge ZJ, Liang QX, Hou Y, Han ZM, Schatten H, Sun QY, Zhang CL (2014) Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice. Reprod Biol Endocrinol 12:29PubMedPubMedCentralCrossRefGoogle Scholar
  45. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One 5:e13100PubMedPubMedCentralCrossRefGoogle Scholar
  46. Guibert S, Forne T, Weber M (2012) Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 22:633–641PubMedPubMedCentralCrossRefGoogle Scholar
  47. Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, Surani MA (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339:448–452PubMedCrossRefGoogle Scholar
  48. Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA (2002) Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117:15–23PubMedCrossRefGoogle Scholar
  49. Hamad MF, Dayyih WAA, Laqqan M, AlKhaled Y, Montenarh M, Hammadeh ME (2018) The status of global DNA methylation in the spermatozoa of smokers and non-smokers. Reprod Biomed Online 37:581–589PubMedCrossRefGoogle Scholar
  50. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473–478PubMedPubMedCentralCrossRefGoogle Scholar
  51. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, Serra-Musach J, Iglesias-Platas I, Formiga F, Fernandez AF, Fraga MF, Heath SC, Valencia A, Gut IG, Wang J, Esteller M (2012) Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci 109:10522–10527PubMedCrossRefPubMedCentralGoogle Scholar
  52. Iqbal K, Tran DA, Li AX, Warden C, Bai AY, Singh P, Wu X, Pfeifer GP, Szabó PE (2015) Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming. Genom Biol 16:59CrossRefGoogle Scholar
  53. Jenkins TG, Aston KI, Pflueger C, Cairns BR, Carrell DT (2014) Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet 10:e1004458PubMedPubMedCentralCrossRefGoogle Scholar
  54. Jenkins TG, James ER, Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, Cairns BR, Carrell DT, Aston KI (2017) Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology 5:1089–1099PubMedPubMedCentralCrossRefGoogle Scholar
  55. Jodar M, Selvaraju S, Sendler E, Diamond MP, Krawetz SA (2013) The presence, role and clinical use of spermatozoal RNAs. Hum Reprod Update 19:604–624Google Scholar
  56. Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M (2013) Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J 32:340–353PubMedCrossRefPubMedCentralGoogle Scholar
  57. Kelly TLJ, Li E, Trasler JM (2003) 5-Aza-2′-Deoxycytidine induces alterations in murine spermatogenesis and pregnancy outcome. J Androl 24:822–830PubMedCrossRefGoogle Scholar
  58. Kerjean A, Dupont JM, Vasseur C, Le Tessier D, Cuisset L, Pàldi A, Jouannet P, Jeanpierre M (2000) Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis. Hum Mol Genet 9:2183–2187PubMedCrossRefGoogle Scholar
  59. Kota SK, Feil R (2010) Epigenetic transitions in germ cell development and meiosis. Dev Cell 19:675–686PubMedCrossRefGoogle Scholar
  60. Krausz C, Sandoval J, Sayols S, Chianese C, Giachini C, Heyn H, Esteller M (2012) Novel insights into DNA methylation features in spermatozoa: stability and peculiarities. PLoS One 7:e44479PubMedPubMedCentralCrossRefGoogle Scholar
  61. Lambrot R, Xu C, Saint-Phar S, Chountalos G, Cohen T, Paquet M, Suderman M, Hallett M, Kimmins S (2013) Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat Commun 4:2889PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88–93PubMedCrossRefPubMedCentralGoogle Scholar
  63. Laqqan M, Tierling S, Alkhaled Y, Porto CL, Solomayer EF, Hammadeh ME (2017) Aberrant DNA methylation patterns of human spermatozoa in current smoker males. Reprod Toxicol 71:126–133PubMedCrossRefPubMedCentralGoogle Scholar
  64. Lee DH (2002) Oxidative DNA damage induced by copper and hydrogen peroxide promotes CG -->TT tandem mutations at methylated CpG dinucleotides in nucleotide excision repair-deficient cells. Nucleic Acids Res 30:3566–3573PubMedPubMedCentralCrossRefGoogle Scholar
  65. Liang F, Diao L, Liu J, Jiang N, Zhang J, Wang H, Zhou W, Huang G, Ma D (2014) Paternal ethanol exposure and behavioral abnormities in offspring: associated alterations in imprinted gene methylation. Neuropharmacology 81:126–133PubMedCrossRefPubMedCentralGoogle Scholar
  66. Lim SO, Gu JM, Kim MS, Kim HS, Park YN, Park CK, Cho JW, Park YM, Jung G (2008) Epigenetic changes induced by reactive oxygen species in hepatocellular carcinoma: methylation of the E-cadherin promoter. Gastroenterology 135:2128–2140PubMedCrossRefPubMedCentralGoogle Scholar
  67. Liu Q, Liu L, Zhao Y, Zhang J, Wang D, Chen J, He Y, Wu J, Zhang Z, Liu Z (2011) Hypoxia induces genomic DNA demethylation through the activation of HIF-1 and transcriptional upregulation of MAT2A in hepatoma cells. Mol Cancer Ther 10:1113–1123PubMedCrossRefPubMedCentralGoogle Scholar
  68. Liu WM, Pang RTK, Chiu PCN, Wong BPC, Lao K, Lee KF, Yeung WSB (2012) Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc Natl Acad Sci 109:490–494PubMedCrossRefPubMedCentralGoogle Scholar
  69. Liu C, Duan W, Li R, Xu S, Zhang L, Chen C, He M, Lu Y, Wu H, Pi H, Luo X, Zhang Y, Zhong M, Yu Z, Zhou Z (2013) Exposure to bisphenol a disrupts meiotic progression during spermatogenesis in adult rats through estrogen-like activity. Cell Death Dis 4:e676PubMedPubMedCentralCrossRefGoogle Scholar
  70. Long L, Wang J, Lu X, Xu Y, Zheng S, Luo C, Li Y (2015) Protective effects of scutellarin on type II diabetes mellitus-induced testicular damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen species/microcirculation/staving pathway in diabetic rat. J Diabetes Res 2015:252530PubMedPubMedCentralCrossRefGoogle Scholar
  71. Long L, Qiu H, Cai B, Chen N, Lu X, Zheng S, Ye X, Li Y (2018) Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget 9:5321–5336PubMedPubMedCentralCrossRefGoogle Scholar
  72. Luo LF, Hou CC, Yang WX (2015) Small non-coding RNAs and their associated proteins in spermatogenesis. Gene 578:141–157PubMedCrossRefPubMedCentralGoogle Scholar
  73. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2012a) Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One 7:e46249PubMedPubMedCentralCrossRefGoogle Scholar
  74. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2012b) Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations. Reprod Toxicol 34:708–719PubMedPubMedCentralCrossRefGoogle Scholar
  75. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK, Gounon P (2013) Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One 8:e55387PubMedPubMedCentralCrossRefGoogle Scholar
  76. Martínez D, Pentinat T, Ribó S, Daviaud C, Bloks VW, Cebrià J, Villalmanzo N, Kalko SG, Ramón-Krauel M, Díaz R, Plösch T, Tost J, Jiménez-Chillarón JC (2014) In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation. Cell Metab 19:941–951PubMedCrossRefPubMedCentralGoogle Scholar
  77. Martini AC, Molina RI, Estofán D, Senestrari D, Fiol De Cuneo M, Ruiz RD (2004) Effects of alcohol and cigarette consumption on human seminal quality. Fertil Steril 82:374–377PubMedCrossRefGoogle Scholar
  78. Mateescu B, Batista L, Cardon M, Gruosso T, De Feraudy Y, Mariani O, Nicolas A, Meyniel JP, Cottu P, Sastre-Garau X, Mechta-Grigoriou F (2011) miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat Med 17:1627–1635PubMedCrossRefPubMedCentralGoogle Scholar
  79. McGraw S, Zhang JX, Farag M, Chan D, Caron M, Konermann C, Oakes CC, Mohan KN, Plass C, Pastinen T, Bourque G, Chaillet JR, Trasler JM (2015) Transient DNMT1 suppression reveals hidden heritable marks in the genome. Nucleic Acids Res 43:1485–1497PubMedPubMedCentralCrossRefGoogle Scholar
  80. McPherson NO, Owens JA, Fullston T, Lane M (2015) Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring. Am J Physiol Endocrinol Metab 308:E805–E821PubMedCrossRefPubMedCentralGoogle Scholar
  81. Miao M, Zhou X, Li Y, Zhang O, Zhou Z, Li T, Yuan W, Li R, Li DKK (2014) LINE-1 hypomethylation in spermatozoa is associated with Bisphenol A exposure. Andrology 2:138–144PubMedCrossRefGoogle Scholar
  82. Milekic MH, Xin Y, O’Donnell A, Kumar KK, Bradley-Moore M, Malaspina D, Moore H, Brunner D, Ge Y, Edwards J, Paul S, Haghighi FG, Gingrich J a (2014) Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression. Mol Psychiatry 20:1–7Google Scholar
  83. Molaro A, Hodges E, Fang F, Song Q, McCombie WR, Hannon GJ, Smith AD (2011) Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 146:1029–1041PubMedPubMedCentralCrossRefGoogle Scholar
  84. Oakes CC, Smiraglia DJ, Plass C, Trasler JM, Robaire B (2003) Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats. Proc Natl Acad Sci U S A 100:1775–1780PubMedPubMedCentralCrossRefGoogle Scholar
  85. Oliva R, Castillo J, Estanyol J, Ballescà J (2015) Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility. Asian J Androl 17:601PubMedPubMedCentralCrossRefGoogle Scholar
  86. Ouko LA, Shantikumar K, Knezovich J, Haycock P, Schnugh DJ, Ramsay M (2009) 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 33:1615–1627PubMedCrossRefGoogle Scholar
  87. Pantano L, Jodar M, Bak M, Ballescà JL, Tommerup N, Oliva R, Vavouri T (2015) The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. RNA 21:1085–1095PubMedPubMedCentralCrossRefGoogle Scholar
  88. Pathak S, Kedia-Mokashi N, Saxena M, D’Souza R, Maitra A, Parte P, Gill-Sharma M, Balasinor N (2009) Effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 locus-specific DNA methylation in rat spermatozoa and its association with embryo loss. Fertil Steril 91:2253–2263PubMedCrossRefGoogle Scholar
  89. Radford EJ, Ito M, Shi H, Corish JA, Yamazawa K, Isganaitis E, Seisenberger S, Hore TA, Reik W, Erkek S, Peters AH, Patti ME, Ferguson-Smith AC (2014) In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science 345:1255903PubMedPubMedCentralCrossRefGoogle Scholar
  90. Rahman MB, Kamal MM, Rijsselaere T, Vandaele L, Shamsuddin M, Van Soom A (2014) 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 26:1107–1116PubMedCrossRefGoogle Scholar
  91. Röther S, Meister G (2011) Small RNAs derived from longer non-coding RNAs. Biochimie 93:1905–1915PubMedCrossRefPubMedCentralGoogle Scholar
  92. Salas-Huetos A, Blanco J, Vidal F, Mercader JM, Garrido N, Anton E (2014) New insights into the expression profile and function of micro-ribonucleic acid in human spermatozoa. Fertil Steril 102:213–222PubMedCrossRefPubMedCentralGoogle Scholar
  93. Salian S, Doshi T, Vanage G (2011) Perinatal exposure of rats to Bisphenol A affects fertility of male offspring-an overview. Reprod Toxicol 31:359–362PubMedCrossRefPubMedCentralGoogle Scholar
  94. Sasaki H, Matsui Y (2008) Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 2008:129–140CrossRefGoogle Scholar
  95. Satta R, Maloku E, Zhubi A, Pibiri F, Hajos M, Costa E, Guidotti A (2008) Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons. Proc Natl Acad Sci 105:16356–16361PubMedCrossRefPubMedCentralGoogle Scholar
  96. Schagdarsurengin U, Steger K (2016) Epigenetics in male reproduction: effect of paternal diet on sperm quality and offspring health. Nat Rev Urol 13:584–595PubMedCrossRefPubMedCentralGoogle Scholar
  97. Schagdarsurengin U, Paradowska A, Steger K (2012) Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction. Nat Rev Urol:1–11Google Scholar
  98. Seisenberger S, Andrews S, Krueger F, Arand J, Walter JJJ, Santos FF, Popp C, Thienpont B, Dean W, Reik W (2012) The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48:849–862PubMedPubMedCentralCrossRefGoogle Scholar
  99. Shnorhavorian M, Schwartz SM, Stansfeld B, Sadler-Riggleman I, Beck D, Skinner MK (2017) Differential DNA methylation regions in adult human sperm following adolescent chemotherapy: potential for epigenetic inheritance. PLoS One 12:e0170085PubMedPubMedCentralCrossRefGoogle Scholar
  100. Simone NL, Soule BP, Ly D, Saleh AD, Savage JE, DeGraff W, Cook J, Harris CC, Gius D, Mitchell JB (2009) Ionizing radiation-induced oxidative stress alters miRNA expression. PLoS One 4:e6377PubMedPubMedCentralCrossRefGoogle Scholar
  101. Skinner MK (2008) What is an epigenetic transgenerational phenotype?. F3 or F2. Reprod Toxicol 25:2–6PubMedCrossRefPubMedCentralGoogle Scholar
  102. Song R, Hennig GW, Wu Q, Jose C, Zheng H, Yan W (2011) Male germ cells express abundant endogenous siRNAs. Proc Natl Acad Sci U S A 108:13159–13164PubMedPubMedCentralCrossRefGoogle Scholar
  103. Soubry A, Guo L, Huang Z, Hoyo C, Romanus S, Price T, Murphy SK (2016) Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics 8:51PubMedPubMedCentralCrossRefGoogle Scholar
  104. Stouder C, Paoloni-Giacobino A (2010) Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm. Reproduction 139:373–379PubMedCrossRefPubMedCentralGoogle Scholar
  105. Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J, Blelloch R (2010) MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol 20:271–277PubMedPubMedCentralCrossRefGoogle Scholar
  106. Sultana S, Zulkifle M, Ansari A, Shahnawaz (2015) Efficacy of local application of an Unani formulation in acne vulgaris. Anc Sci Life 35:124PubMedPubMedCentralCrossRefGoogle Scholar
  107. Tang WWC, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR, Hackett JA, Chinnery PF, Surani MA (2015) A unique gene regulatory network resets the human germline epigenome for development. Cell 161:1453–1467PubMedPubMedCentralCrossRefGoogle Scholar
  108. Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C, Greally JM, Barzilai N (2010) Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9:506–518PubMedPubMedCentralCrossRefGoogle Scholar
  109. Tiwari D, Vanage G (2013) Mutagenic effect of Bisphenol A on adult rat male germ cells and their fertility. Reprod Toxicol 40:60–68PubMedCrossRefPubMedCentralGoogle Scholar
  110. Tracey R, Manikkam M, Guerrero-Bosagna C, Skinner MK (2013) Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. Reprod Toxicol 36:104–116PubMedPubMedCentralCrossRefGoogle Scholar
  111. Van Der Heijden GW, Ramos L, Baart EB, Van Den Berg IM, Derijck AA, Van Der Vlag J, Martini E, De Boer P (2008) Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol 8:34PubMedPubMedCentralCrossRefGoogle Scholar
  112. Vrooman LA, Oatley JM, Griswold JE, Hassold TJ, Hunt PA (2015) Estrogenic exposure alters the spermatogonial stem cells in the developing testis, permanently reducing crossover levels in the adult. PLoS Genet 11:e1004949PubMedPubMedCentralCrossRefGoogle Scholar
  113. Wei Y, Yang CR, Wei YP, Zhao ZA, Hou Y, Schatten H, Sun QY (2014) Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A 111:1873–1878PubMedPubMedCentralCrossRefGoogle Scholar
  114. Xue J, Schoenrock SA, Valdar W, Tarantino LM, Ideraabdullah FY (2016) Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clin Epigenetics 8:107PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Joan Blanco Rodríguez
    • 1
    Email author
  • Cristina Camprubí Sánchez
    • 2
    • 3
    • 4
  1. 1.Genetics of Male Fertility Group, Unitat de Biologia Cel·lular (Facultat de Biociències)Universitat Autònoma de BarcelonaBellaterra (Cerdanyola del Vallès)Spain
  2. 2.GenIntegralBarcelonaSpain
  3. 3.Reference Laboratory GeneticsL’Hospitalet de LlobregatSpain
  4. 4.Unitat de Biologia Cel·lular i Genètica Mèdica (Facultat de Medicina)Universitat Autònoma de BarcelonaBellaterra (Cerdanyola del Vallès)Spain

Personalised recommendations