Advertisement

Paternal Obesity and Programming of Offspring Health

  • Tod Fullston
  • Helana S. Shehadeh
  • John E. Schjenken
  • Nicole O. McPherson
  • Sarah A. Robertson
  • Deirdre Zander-Fox
  • Michelle Lane
Chapter
Part of the Physiology in Health and Disease book series (PIHD)

Abstract

The physical and nutritional environment experienced by the mother prior to and during conception is imperative to the outcome of pregnancy and offspring health. In addition, there is now mounting evidence that paternal exposures and conditions at the time of conception are also an important determinant of pregnancy outcome and offspring health. Specifically, male obesity is now demonstrated to have detrimental impacts on fertility and fetal development during subsequent pregnancy and can exert programming effects on the phenotype of offspring lasting up to two generations. We summarise the evidence of the effect of environmental exposures on seminal plasma and sperm, focusing on the effects of obesity, and what bearing this has for offspring both in humans and animal models. The current knowledge of what might form the molecular basis of the phenomena of paternal programming of offspring health is also reviewed with consideration given to signals from both seminal plasma and sperm.

Keywords

Paternal non-genetic transmission Epigenetics Sperm Seminal fluid Programming Obesity Environmental exposure Spermatogenesis 

Abbreviations

ROS

Reactive oxygen species

8-OHdG

8-hydroxy-2′-deoxyguanosine (oxidatively damaged Guanosine base)

5mC

5-methyl-Cytosine

5hmC

Hydroxymethyl-Cytosine (oxidised form of 5mC)

NOX

NAPDH oxidase

OGG1

8-Oxoguanine glycosylase (enzyme)

BMI

Body mass index

SVX

Seminal vesicle deficient (mouse model)

sncRNA

Small non-coding RNA

References

  1. 1.
    Guerriero G, Trocchia S, Abdel-Gawad FK, Ciarcia G (2014) Roles of reactive oxygen species in the spermatogenesis regulation. Front Endocrinol 5:56, Pubmed Central PMCID: 4001055CrossRefGoogle Scholar
  2. 2.
    Mendis-Handagama SM (1997) Luteinizing hormone on Leydig cell structure and function. Histol Histopathol 12(3):869–882PubMedGoogle Scholar
  3. 3.
    Ho HC (2010) Redistribution of nuclear pores during formation of the redundant nuclear envelope in mouse spermatids. J Anat 216(4):525–532, Pubmed Central PMCID: 2849530PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Rengan AK, Agarwal A, van der Linde M, du Plessis SS (2012) An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet. Reprod Biol Endocrinol 10:92, Pubmed Central PMCID: 3551780PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Sprando RL, Russell LD (1987) Comparative study of cytoplasmic elimination in spermatids of selected mammalian species. Am J Anat 178(1):72–80PubMedCrossRefGoogle Scholar
  6. 6.
    Cooper TG (2011) The epididymis, cytoplasmic droplets and male fertility. Asian J Androl 13(1):130–138, Pubmed Central PMCID: 3739406PubMedCrossRefGoogle Scholar
  7. 7.
    Sharpe RM (2010) Environmental/lifestyle effects on spermatogenesis. Philos Trans R Soc Lond B Biol Sci 365(1546):1697–1712, Pubmed Central PMCID: 2871918PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R (2013) Chromatin dynamics during spermiogenesis. Biochim Biophys Acta 1839(3):155–168PubMedCrossRefGoogle Scholar
  9. 9.
    Dadoune JP (1995) The nuclear status of human sperm cells. Micron 26(4):323–345PubMedCrossRefGoogle Scholar
  10. 10.
    Braun RE (2001) Packaging paternal chromosomes with protamine. Nat Genet 28(1):10–12PubMedGoogle Scholar
  11. 11.
    Miller D, Brinkworth M, Iles D (2010) Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction 139(2):287–301PubMedCrossRefGoogle Scholar
  12. 12.
    Kowalski A, Palyga J (2012) Linker histone subtypes and their allelic variants. Cell Biol Int 36(11):981–996PubMedCrossRefGoogle Scholar
  13. 13.
    Godmann M, Auger V, Ferraroni-Aguiar V, Di Sauro A, Sette C, Behr R et al (2007) Dynamic regulation of histone H3 methylation at lysine 4 in mammalian spermatogenesis. Biol Reprod 77(5):754–764PubMedCrossRefGoogle Scholar
  14. 14.
    Moriniere J, Rousseaux S, Steuerwald U, Soler-Lopez M, Curtet S, Vitte AL et al (2009) Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461(7264):664–668PubMedCrossRefGoogle Scholar
  15. 15.
    Chen HY, Sun JM, Zhang Y, Davie JR, Meistrich ML (1998) Ubiquitination of histone H3 in elongating spermatids of rat testes. J Biol Chem 273(21):13165–13169PubMedCrossRefGoogle Scholar
  16. 16.
    Brewer L, Corzett M, Balhorn R (2002) Condensation of DNA by spermatid basic nuclear proteins. J Biol Chem 277(41):38895–38900PubMedCrossRefGoogle Scholar
  17. 17.
    Kierszenbaum AL (2001) Transition nuclear proteins during spermiogenesis: unrepaired DNA breaks not allowed. Mol Reprod Dev 58(4):357–358PubMedCrossRefGoogle Scholar
  18. 18.
    Brewer LR, Corzett M, Balhorn R (1999) Protamine-induced condensation and decondensation of the same DNA molecule. Science 286(5437):120–123PubMedCrossRefGoogle Scholar
  19. 19.
    Carrell DT, Emery BR, Hammoud S (2007) Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update 13(3):313–327PubMedCrossRefGoogle Scholar
  20. 20.
    Garrido N, Remohi J, Martinez-Conejero JA, Garcia-Herrero S, Pellicer A, Meseguer M (2008) Contribution of sperm molecular features to embryo quality and assisted reproduction success. Reprod Biomed Online 17(6):855–865PubMedCrossRefGoogle Scholar
  21. 21.
    Carrell DT, Hammoud SS (2010) The human sperm epigenome and its potential role in embryonic development. Mol Hum Reprod 16(1):37–47PubMedCrossRefGoogle Scholar
  22. 22.
    Yan W (2009) Male infertility caused by spermiogenic defects: lessons from gene knockouts. Mol Cell Endocrinol 306(1–2):24–32PubMedCrossRefGoogle Scholar
  23. 23.
    Dacheux JL, Dacheux F (2014) New insights into epididymal function in relation to sperm maturation. Reproduction 147(2):R27–R42PubMedCrossRefGoogle Scholar
  24. 24.
    Ariel M, Cedar H, McCarrey J (1994) Developmental changes in methylation of spermatogenesis-specific genes include reprogramming in the epididymis. Nat Genet 7(1):59–63PubMedCrossRefGoogle Scholar
  25. 25.
    Belleannee C (2015) Extracellular microRNAs from the epididymis as potential mediators of cell-to-cell communication. Asian J Androl 17(5):730–736PubMedPubMedCentralGoogle Scholar
  26. 26.
    Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Tyagi S et al (2015) The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation. Biol Reprod 93(4):91PubMedCrossRefGoogle Scholar
  27. 27.
    O’Donnell L, Nicholls PK, O’Bryan MK, McLachlan RI, Stanton PG (2011) Spermiation: the process of sperm release. Spermatogenesis 1(1):14–35, Pubmed Central PMCID: 3158646PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Solomon B, Duncan M (2007) Proteomics of seminal fluid. Proteomics of human body fluids—principles, methods and applications. Humana Press, Totowa, NJ, pp 467–493CrossRefGoogle Scholar
  29. 29.
    Arienti G, Saccardi C, Carlini E, Verdacchi R, Palmerini CA (1999) Distribution of lipid and protein in human semen fractions. Clin Chim Acta 289(1–2):111–120PubMedCrossRefGoogle Scholar
  30. 30.
    Ronquist G, Brody I (1985) The prostasome: its secretion and function in man. Biochim Biophys Acta 822(2):203–218PubMedCrossRefGoogle Scholar
  31. 31.
    Poiani A (2006) Complexity of seminal fluid: a review. Behav Ecol Sociobiol 60(3):289–310, PubMed PMID: WOS:000238453700001. EnglishCrossRefGoogle Scholar
  32. 32.
    Park KH, Kim BJ, Kang J, Nam TS, Lim JM, Kim HT et al (2011) Ca2+ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility. Sci Signal 4(173):ra31PubMedCrossRefGoogle Scholar
  33. 33.
    Pons-Rejraji H, Artonne C, Sion B, Brugnon F, Canis M, Janny L et al (2011) Prostasomes: inhibitors of capacitation and modulators of cellular signalling in human sperm. Int J Androl 34(6 Pt 1):568–580PubMedCrossRefGoogle Scholar
  34. 34.
    Ronquist G (2012) Prostasomes are mediators of intercellular communication: from basic research to clinical implications. J Intern Med 271(4):400–413PubMedCrossRefGoogle Scholar
  35. 35.
    Aumuller G, Riva A (1992) Morphology and functions of the human seminal vesicle. Andrologia 24(4):183–196PubMedCrossRefGoogle Scholar
  36. 36.
    Maegawa M, Kamada M, Irahara M, Yamamoto S, Yoshikawa S, Kasai Y et al (2002) A repertoire of cytokines in human seminal plasma. J Reprod Immunol 54(1–2):33–42PubMedCrossRefGoogle Scholar
  37. 37.
    Mann T (1964) The biochemistry of semen and the male reproductive tract. Wiley, New YorkGoogle Scholar
  38. 38.
    Schjenken JE, Glynn DJ, Sharkey DJ, Robertson SA (2015) TLR4 signaling is a major mediator of the female tract response to seminal fluid in mice. Biol Reprod 93(3):68PubMedCrossRefGoogle Scholar
  39. 39.
    Schjenken JE, Robertson SA (2014) Seminal fluid and immune adaptation for pregnancy—comparative biology in mammalian species. Reprod Domest Anim 49(Suppl 3):27–36PubMedCrossRefGoogle Scholar
  40. 40.
    Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA (2012) Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 188(5):2445–2454PubMedCrossRefGoogle Scholar
  41. 41.
    Bromfield JJ, Schjenken JE, Chin PY, Care AS, Jasper MJ, Robertson SA (2014) Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc Natl Acad Sci USA 111(6):2200–2205, Pubmed Central PMCID: 3926084PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Chong S, Whitelaw E (2004) Epigenetic germline inheritance. Curr Opin Genet Dev 14(6):692–696PubMedCrossRefGoogle Scholar
  43. 43.
    Brykczynska U, Hisano M, Erkek S, Ramos L, Oakeley EJ, Roloff TC et al (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17(6):679–687PubMedCrossRefGoogle Scholar
  44. 44.
    Brunner AM, Nanni P, Mansuy IM (2014) Epigenetic marking of sperm by post-translational modification of histones and protamines. Epigenetics Chromatin 7(1):2, Pubmed Central PMCID: 3904194PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Noblanc A, Damon-Soubeyrand C, Karrich B, Henry-Berger J, Cadet R, Saez F et al (2013) DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected? Free Radic Biol Med 65:719–723PubMedCrossRefGoogle Scholar
  46. 46.
    Gannon JR, Emery BR, Jenkins TG, Carrell DT (2014) The sperm epigenome: implications for the embryo. Adv Exp Med Biol 791:53–66PubMedCrossRefGoogle Scholar
  47. 47.
    Ward WS (2010) Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod 16(1):30–36, Pubmed Central PMCID: 2790366PubMedCrossRefGoogle Scholar
  48. 48.
    Schneider G, Kirschner MA, Berkowitz R, Ertel NH (1979) Increased estrogen production in obese men. J Clin Endocrinol Metab 48(4):633–638, Epub 1979/04/01. engPubMedCrossRefGoogle Scholar
  49. 49.
    Kley HK, Deselaers T, Peerenboom H (1981) Evidence for hypogonadism in massively obese males due to decreased free testosterone. Horm Metab Res 13(11):639–641, Epub 1981/11/01. engPubMedCrossRefGoogle Scholar
  50. 50.
    Jarow JP, Kirkland J, Koritnik DR, Cefalu WT (1993) Effect of obesity and fertility status on sex steroid levels in men. Urology 42(2):171–174, Epub 1993/08/01. engPubMedCrossRefGoogle Scholar
  51. 51.
    MacDonald AA, Herbison GP, Showell M, Farquhar CM (2010) The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 16(3):293–311, Epub 2009/11/06. engPubMedCrossRefGoogle Scholar
  52. 52.
    Jensen TK, Andersson AM, Jorgensen N, Andersen AG, Carlsen E, Petersen JH et al (2004) Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 82(4):863–870, Epub 2004/10/16. engPubMedCrossRefGoogle Scholar
  53. 53.
    Fejes I, Koloszar S, Szollosi J, Zavaczki Z, Pal A (2005) Is semen quality affected by male body fat distribution? Andrologia 37(5):155–159, Epub 2005/11/04. engPubMedCrossRefGoogle Scholar
  54. 54.
    Hammoud AO, Wilde N, Gibson M, Parks A, Carrell DT, Meikle AW (2008) Male obesity and alteration in sperm parameters. Fertil Steril 90(6):2222–2225, Epub 2008/01/08. engPubMedCrossRefGoogle Scholar
  55. 55.
    Bakos HW, Henshaw RC, Mitchell M, Lane M (2011) Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil Steril 95(5):1700–1704PubMedCrossRefGoogle Scholar
  56. 56.
    Kort HI, Massey JB, Elsner CW, Mitchell-Leef D, Shapiro DB, Witt MA et al (2006) Impact of body mass index values on sperm quantity and quality. J Androl 27(3):450–452, Epub 2005/12/13. engPubMedCrossRefGoogle Scholar
  57. 57.
    Chavarro JE, Toth TL, Wright DL, Meeker JD, Hauser R (2010) Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril 93(7):2222–2231, Pubmed Central PMCID: 2864498, Epub 2009/03/06. engPubMedCrossRefGoogle Scholar
  58. 58.
    Pauli EM, Legro RS, Demers LM, Kunselman AR, Dodson WC, Lee PA (2008) Diminished paternity and gonadal function with increasing obesity in men. Fertil Steril 90(2):346–351, Pubmed Central PMCID: 2597471, Epub 2008/02/23. engPubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Aggerholm AS, Thulstrup AM, Toft G, Ramlau-Hansen CH, Bonde JP (2008) Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile? Fertil Steril 90(3):619–626PubMedCrossRefGoogle Scholar
  60. 60.
    Rybar R, Kopecka V, Prinosilova P, Markova P, Rubes J (2011) Male obesity and age in relationship to semen parameters and sperm chromatin integrity. Andrologia 43(4):286–291PubMedCrossRefGoogle Scholar
  61. 61.
    Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK et al (2013) BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update 19(3):221–231, Pubmed Central PMCID: 3621293PubMedCrossRefGoogle Scholar
  62. 62.
    Campbell J, Lane M, Owens JA, Bakos HW (2015) Paternal obesity negatively affects fertility and assisted reproduction outcomes: a systematic review and meta-analysis. Reprod Biomed Online 31(5):593–604PubMedCrossRefGoogle Scholar
  63. 63.
    Kovac JR, Khanna A, Lipshultz LI (2015) The effects of cigarette smoking on male fertility. Postgrad Med 127(3):338–341PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Practice Committee of the American Society for Reproductive M (2012) Smoking and infertility: a committee opinion. Fertil Steril 98(6):1400–1406CrossRefGoogle Scholar
  65. 65.
    Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN (1996) Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res 351(2):199–203PubMedCrossRefGoogle Scholar
  66. 66.
    Ji BT, Shu XO, Linet MS, Zheng W, Wacholder S, Gao YT et al (1997) Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers. J Natl Cancer Inst 89(3):238–244PubMedCrossRefGoogle Scholar
  67. 67.
    Trasler JM (2009) Epigenetics in spermatogenesis. Mol Cell Endocrinol 306(1–2):33–36PubMedCrossRefGoogle Scholar
  68. 68.
    Linschooten JO, Verhofstad N, Gutzkow K, Olsen AK, Yauk C, Oligschlager Y et al (2013) Paternal lifestyle as a potential source of germline mutations transmitted to offspring. FASEB J 27(7):2873–2879, Pubmed Central PMCID: 3688758PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Johnson SL, Dunleavy J, Gemmell NJ, Nakagawa S (2015) Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev 19:22–33PubMedCrossRefGoogle Scholar
  70. 70.
    Sartorelli EM, Mazzucatto LF, de Pina-Neto JM (2001) Effect of paternal age on human sperm chromosomes. Fertil Steril 76(6):1119–1123PubMedCrossRefGoogle Scholar
  71. 71.
    Singh NP, Muller CH, Berger RE (2003) Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril 80(6):1420–1430PubMedCrossRefGoogle Scholar
  72. 72.
    Vagnini L, Baruffi RL, Mauri AL, Petersen CG, Massaro FC, Pontes A et al (2007) The effects of male age on sperm DNA damage in an infertile population. Reprod Biomed Online 15(5):514–519PubMedCrossRefGoogle Scholar
  73. 73.
    Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G et al (2012) Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488(7412):471–475, Pubmed Central PMCID: 3548427PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S et al (2006) Advancing paternal age and autism. Arch Gen Psychiatry 63(9):1026–1032PubMedCrossRefGoogle Scholar
  75. 75.
    Perrin MC, Brown AS, Malaspina D (2007) Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia. Schizophr Bull 33(6):1270–1273, Pubmed Central PMCID: 2779878PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Maconochie N, Doyle P, Prior S, Simmons R (2007) Risk factors for first trimester miscarriage—results from a UK-population-based case-control study. BJOG 114(2):170–186PubMedCrossRefGoogle Scholar
  77. 77.
    Nybo Andersen AM, Hansen KD, Andersen PK, Davey Smith G (2004) Advanced paternal age and risk of fetal death: a cohort study. Am J Epidemiol 160(12):1214–1222PubMedCrossRefGoogle Scholar
  78. 78.
    Harlap S, Paltiel O, Deutsch L, Knaanie A, Masalha S, Tiram E et al (2002) Paternal age and preeclampsia. Epidemiology 13(6):660–667PubMedCrossRefGoogle Scholar
  79. 79.
    Shah PS (2010) Knowledge synthesis group on determinants of LBWPTb. Parity and low birth weight and preterm birth: a systematic review and meta-analyses. Acta Obstet Gynecol Scand 89(7):862–875PubMedCrossRefGoogle Scholar
  80. 80.
    Zammit S, Allebeck P, Dalman C, Lundberg I, Hemmingson T, Owen MJ et al (2003) Paternal age and risk for schizophrenia. Br J Psychiatry 183:405–408PubMedCrossRefGoogle Scholar
  81. 81.
    Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Langstrom N, Hultman CM (2008) Advancing paternal age and bipolar disorder. Arch Gen Psychiatry 65(9):1034–1040PubMedCrossRefGoogle Scholar
  82. 82.
    Naserbakht M, Ahmadkhaniha HR, Mokri B, Smith CL (2011) Advanced paternal age is a risk factor for schizophrenia in Iranians. Ann General Psychiatry 10:15, Pubmed Central PMCID: 3094249CrossRefGoogle Scholar
  83. 83.
    Sartorius GA, Nieschlag E (2010) Paternal age and reproduction. Hum Reprod Update 16(1):65–79PubMedCrossRefGoogle Scholar
  84. 84.
    El-Helaly M, Abdel-Elah K, Haussein A, Shalaby H (2011) Paternal occupational exposures and the risk of congenital malformations—a case-control study. Int J Occup Med Environ Health 24(2):218–227PubMedCrossRefGoogle Scholar
  85. 85.
    van Balkom ID, Bresnahan M, Vuijk PJ, Hubert J, Susser E, Hoek HW (2012) Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: Aruba. PLoS One 7(9), e45090, Pubmed Central PMCID: 3439376PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Lee KM, Ward MH, Han S, Ahn HS, Kang HJ, Choi HS et al (2009) Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk. Leuk Res 33(2):250–258, Pubmed Central PMCID: 2787091PubMedCrossRefGoogle Scholar
  87. 87.
    Ng SF, Lin RC, Maloney CA, Youngson NA, Owens JA, Morris MJ (2014) Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring. FASEB J 28(4):1830–1841PubMedCrossRefGoogle Scholar
  88. 88.
    Australian Bureau of Statistics (2015) National Health Survey: Overweight and obesity. Report 4364.0.55. http://www.abs.gov.au/ausstats/abs@.nsf/mf/4364.0.55.001
  89. 89.
    Keltz J, Zapantis A, Jindal SK, Lieman HJ, Santoro N, Polotsky AJ (2010) Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. J Assist Reprod Genet 27(9–10):539–544, Pubmed Central PMCID: 2965348, Epub 2010/07/17. engPubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Hinz S, Rais-Bahrami S, Kempkensteffen C, Weiske WH, Miller K, Magheli A (2010) Effect of obesity on sex hormone levels, antisperm antibodies, and fertility after vasectomy reversal. Urology 76(4):851–856, Epub 2010/05/01. engPubMedCrossRefGoogle Scholar
  91. 91.
    Merhi ZO, Keltz J, Zapantis A, Younger J, Berger D, Lieman HJ et al (2013) Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality. Obesity (Silver Spring) 21(8):1608–1612CrossRefGoogle Scholar
  92. 92.
    Ramasamy R, Bryson C, Reifsnyder JE, Neri Q, Palermo GD, Schlegel PN (2013) Overweight men with nonobstructive azoospermia have worse pregnancy outcomes after microdissection testicular sperm extraction. Fertil Steril 99(2):372–376PubMedCrossRefGoogle Scholar
  93. 93.
    Colaci DS, Afeiche M, Gaskins AJ, Wright DL, Toth TL, Tanrikut C et al (2012) Men’s body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization. Fertil Steril 98(5):1193–1199e1, Pubmed Central PMCID: 3478419PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Mitchell M, Bakos HW, Lane M (2011) Paternal diet-induced obesity impairs embryo development and implantation in the mouse. Fertil Steril 95(4):1349–1353, Epub 2010/11/05. engPubMedCrossRefGoogle Scholar
  95. 95.
    McPherson NO, Bakos HW, Owens JA, Setchell BP, Lane M (2013) Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth. PLoS One 8(8):e71459, Pubmed Central PMCID: 3747240PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Lane M, McPherson NO, Fullston T, Spillane M, Sandeman L, Kang WX et al (2014) Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring. PLoS One 9(7):e100832, Pubmed Central PMCID: 4089912PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Silva PF, Gadella BM, Colenbrander B, Roelen BA (2007) Exposure of bovine sperm to pro-oxidants impairs the developmental competence of the embryo after the first cleavage. Theriogenology 67(3):609–619PubMedCrossRefGoogle Scholar
  98. 98.
    Zorn B, Vidmar G, Meden-Vrtovec H (2003) Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl 26(5):279–285PubMedCrossRefGoogle Scholar
  99. 99.
    Danielzik S, Langnase K, Mast M, Spethmann C, Muller MJ (2002) Impact of parental BMI on the manifestation of overweight 5–7 year old children. Eur J Nutr 41(3):132–138, Epub 2002/07/12. engPubMedCrossRefGoogle Scholar
  100. 100.
    Li L, Law C, Lo Conte R, Power C (2009) Intergenerational influences on childhood body mass index: the effect of parental body mass index trajectories. Am J Clin Nutr 89(2):551–557, Epub 2008/12/25. engPubMedCrossRefGoogle Scholar
  101. 101.
    Ng S-F, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs [bgr]-cell dysfunction in female rat offspring. Nature 467(7318):963–966PubMedCrossRefGoogle Scholar
  102. 102.
    Fullston T, Palmer NO, Owens JA, Mitchell M, Bakos HW, Lane M (2012) Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice. Hum Reprod 27(5):1391–1400, Epub 2012/02/24. engPubMedCrossRefGoogle Scholar
  103. 103.
    Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M et al (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(10):4226–4243PubMedCrossRefGoogle Scholar
  104. 104.
    Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI (2008) Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett 266(1):6–11PubMedCrossRefGoogle Scholar
  105. 105.
    Fleming JL, Phiel CJ, Toland AE (2012) The role for oxidative stress in aberrant DNA methylation in Alzheimer’s disease. Curr Alzheimer Res 9(9):1077–1096PubMedCrossRefGoogle Scholar
  106. 106.
    Palmer NO, Bakos HW, Fullston T, Lane M (2012) Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2(4):253–263, Pubmed Central PMCID: 3521747PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Binder NK, Hannan NJ, Gardner DK (2012) Paternal diet-induced obesity retards early mouse embryo development, mitochondrial activity and pregnancy health. PLoS One 7(12):e52304, Pubmed Central PMCID: 3531483PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Horak S, Polanska J, Widlak P (2003) Bulky DNA adducts in human sperm: relationship with fertility, semen quality, smoking, and environmental factors. Mutat Res 537(1):53–65PubMedCrossRefGoogle Scholar
  109. 109.
    Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313PubMedCrossRefGoogle Scholar
  110. 110.
    Aitken J, Fisher H (1994) Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioessays 16(4):259–267PubMedCrossRefGoogle Scholar
  111. 111.
    Lavranos G, Balla M, Tzortzopoulou A, Syriou V, Angelopoulou R (2012) Investigating ROS sources in male infertility: a common end for numerous pathways. Reprod Toxicol 34(3):298–307PubMedCrossRefGoogle Scholar
  112. 112.
    Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortes MM, Hoang YD et al (2010) Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med 49(9):1368–1379, Pubmed Central PMCID: 2948056PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gharagozloo P, Aitken RJ (2011) The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod 26(7):1628–1640, Epub 2011/05/07. EngPubMedCrossRefGoogle Scholar
  114. 114.
    Zribi N, Chakroun NF, Elleuch H, Abdallah FB, Ben Hamida AS, Gargouri J et al (2011) Sperm DNA fragmentation and oxidation are independent of malondialdheyde. Reprod Biol Endocrinol 9:47, Pubmed Central PMCID: 3098153PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Dada R, Shamsi MB, Venkatesh S, Gupta NP, Kumar R (2010) Attenuation of oxidative stress & DNA damage in varicocelectomy: implications in infertility management. Indian J Med Res 132(6):728–730, Epub 2011/01/20. engPubMedPubMedCentralGoogle Scholar
  116. 116.
    Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human-spermatozoa. J Reprod Fertil 81(2):459–469, PubMed PMID: WOS:A1987K957600020. EnglishPubMedCrossRefGoogle Scholar
  117. 117.
    Aitken RJ (1999) The Amoroso Lecture—the human spermatozoon—a cell in crisis? J Reprod Fertil 115(1):1–7, PubMed PMID: WOS:000078697400001. EnglishPubMedCrossRefGoogle Scholar
  118. 118.
    Aitken RJ, Curry BJ (2011) Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid Redox Signal 14(3):367–381, PubMed PMID: WOS:000285876900004. EnglishPubMedCrossRefGoogle Scholar
  119. 119.
    Saleh RA, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23(6):737–752PubMedGoogle Scholar
  120. 120.
    De Iuliis GN, Thomson LK, Mitchell LA, Finnie JM, Koppers AJ, Hedges A et al (2009) DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress. Biol Reprod 81(3):517–524, PubMed PMID: WOS:000269256400009. EnglishPubMedCrossRefGoogle Scholar
  121. 121.
    Aitken RJ, Baker MA, Sawyer D (2003) Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease. Reprod Biomed Online 7(1):65–70PubMedCrossRefGoogle Scholar
  122. 122.
    Twigg J, Fulton N, Gomez E, Irvine DS, Aitken RJ (1998) Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod 13(6):1429–1436PubMedCrossRefGoogle Scholar
  123. 123.
    Sharma RK, Agarwal A (1996) Role of reactive oxygen species in male infertility. Urology 48(6):835–850PubMedCrossRefGoogle Scholar
  124. 124.
    Sikka SC (2001) Relative impact of oxidative stress on male reproductive function. Curr Med Chem 8(7):851–862PubMedCrossRefGoogle Scholar
  125. 125.
    Hammoud SS, Nix DA, Hammoud AO, Gibson M, Cairns BR, Carrell DT (2011) Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod 26(9):2558–2569, Pubmed Central PMCID: 3157626PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Mitchell LA, De Iuliis GN, Aitken RJ (2011) The TUNEL assay consistently underestimates DNA damage in human spermatozoa and is influenced by DNA compaction and cell vitality: development of an improved methodology. Int J Androl 34(1):2–13PubMedCrossRefGoogle Scholar
  127. 127.
    Barroso G, Morshedi M, Oehninger S (2000) Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod 15(6):1338–1344PubMedCrossRefGoogle Scholar
  128. 128.
    Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T (1997) Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril 68(3):519–524PubMedCrossRefGoogle Scholar
  129. 129.
    Sun JG, Jurisicova A, Casper RF (1997) Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod 56(3):602–607PubMedCrossRefGoogle Scholar
  130. 130.
    Aitken RJ, Baker MA (2004) Oxidative stress and male reproductive biology. Reprod Fertil Dev 16(5):581–588PubMedCrossRefGoogle Scholar
  131. 131.
    Kemal Duru N, Morshedi M, Oehninger S (2000) Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril 74(6):1200–1207PubMedCrossRefGoogle Scholar
  132. 132.
    Douki T, Odin F, Caillat S, Favier A, Cadet J (2004) Predominance of the 1, N2-propano 2′-deoxyguanosine adduct among 4-hydroxy-2-nonenal-induced DNA lesions. Free Radic Biol Med 37(1):62–70PubMedCrossRefGoogle Scholar
  133. 133.
    Twigg J, Irvine DS, Houston P, Fulton N, Michael L, Aitken RJ (1998) Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol Hum Reprod 4(5):439–445PubMedCrossRefGoogle Scholar
  134. 134.
    Badouard C, Menezo Y, Panteix G, Ravanat JL, Douki T, Cadet J et al (2008) Determination of new types of DNA lesions in human sperm. Zygote 16(1):9–13PubMedCrossRefGoogle Scholar
  135. 135.
    Lopes S, Sun JG, Jurisicova A, Meriano J, Casper RF (1998) Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil Steril 69(3):528–532, Epub 1998/04/09. engPubMedCrossRefGoogle Scholar
  136. 136.
    Tomsu M, Sharma V, Miller D (2002) Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. Hum Reprod 17(7):1856–1862, Epub 2002/07/03. engPubMedCrossRefGoogle Scholar
  137. 137.
    Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A et al (2003) Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril 79(Suppl 3):1597–1605, Epub 2003/06/13. engPubMedCrossRefGoogle Scholar
  138. 138.
    Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D (2004) Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril 82(2):378–383, Epub 2004/08/11. engPubMedCrossRefGoogle Scholar
  139. 139.
    Larson KL, DeJonge CJ, Barnes AM, Jost LK, Evenson DP (2000) Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod 15(8):1717–1722PubMedCrossRefGoogle Scholar
  140. 140.
    Virro MR, Larson-Cook KL, Evenson DP (2004) Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril 81(5):1289–1295PubMedCrossRefGoogle Scholar
  141. 141.
    Aitken RJ, De Iuliis GN, McLachlan RI (2009) Biological and clinical significance of DNA damage in the male germ line. Int J Androl 32(1):46–56PubMedCrossRefGoogle Scholar
  142. 142.
    Kleinhaus K, Perrin M, Friedlander Y, Paltiel O, Malaspina D, Harlap S (2006) Paternal age and spontaneous abortion. Obstet Gynecol 108(2):369–377PubMedCrossRefGoogle Scholar
  143. 143.
    Sipos A, Rasmussen F, Harrison G, Tynelius P, Lewis G, Leon DA et al (2004) Paternal age and schizophrenia: a population based cohort study. BMJ 329(7474):1070, Pubmed Central PMCID: 526116PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Tremellen K (2008) Oxidative stress and male infertility—a clinical perspective. Hum Reprod Update 14(3):243–258PubMedCrossRefGoogle Scholar
  145. 145.
    Xu DX, Shen HM, Zhu QX, Chua L, Wang QN, Chia SE et al (2003) The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res 534(1–2):155–163PubMedCrossRefGoogle Scholar
  146. 146.
    Lee J, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S et al (2007) Akt mediates self-renewal division of mouse spermatogonial stem cells. Development 134(10):1853–1859PubMedCrossRefGoogle Scholar
  147. 147.
    Soubry A, Hoyo C, Jirtle RL, Murphy SK (2014) A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. Bioessays 36(4):359–371, Pubmed Central PMCID: 4047566PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32(14):4100–4108, Pubmed Central PMCID: 514367PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF et al (2015) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond) 39(4):650–657, Pubmed Central PMCID: 4048324CrossRefGoogle Scholar
  150. 150.
    Smith TB, Dun MD, Smith ND, Curry BJ, Connaughton HS, Aitken RJ (2013) The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1. J Cell Sci 126(Pt 6):1488–1497PubMedCrossRefGoogle Scholar
  151. 151.
    Burton GJ, Fowden AL (2012) Review: The placenta and developmental programming: balancing fetal nutrient demands with maternal resource allocation. Placenta 33(Suppl):S23–S27PubMedCrossRefGoogle Scholar
  152. 152.
    Chan OC, Chow PH (2001) O WS. Total ablation of paternal accessory sex glands curtails developmental potential in preimplantation embryos in the golden hamster. Anat Embryol 204(2):117–122PubMedCrossRefGoogle Scholar
  153. 153.
    Wong CL, Chan OC, Lee KH, O WS, Chow PH (2008) Absence of paternal accessory sex glands dysregulates preimplantation embryo cell cycle and causes early oviductal-uterine transit in the golden hamster in vivo. Fertil Steril 89(4):1021–1024PubMedCrossRefGoogle Scholar
  154. 154.
    Ying Y, Chow PH, O WS (1998) Effects of male accessory sex glands on deoxyribonucleic acid synthesis in the first cell cycle of golden hamster embryos. Biol Reprod 58(3):659–663PubMedCrossRefGoogle Scholar
  155. 155.
    Jiang HY, O WS, Lee KH, Tang PL, Chow PH (2001) Ablation of paternal accessory sex glands is detrimental to embryo development during implantation. Anat Embryol 203(4):255–263PubMedCrossRefGoogle Scholar
  156. 156.
    Wong CL, Lee KH, Lo KM, Chan OC, Goggins W, O WS et al (2007) Ablation of paternal accessory sex glands imparts physical and behavioural abnormalities to the progeny: an in vivo study in the golden hamster. Theriogenology 68(4):654–662PubMedCrossRefGoogle Scholar
  157. 157.
    Cottrell EC, Ozanne SE (2008) Early life programming of obesity and metabolic disease. Physiol Behav 94(1):17–28PubMedCrossRefGoogle Scholar
  158. 158.
    Crawford G, Ray A, Gudi A, Shah A, Homburg R (2015) The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum Reprod Update 21(2):275–284PubMedCrossRefGoogle Scholar
  159. 159.
    Tremellen KP, Valbuena D, Landeras J, Ballesteros A, Martinez J, Mendoza S et al (2000) The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 15(12):2653–2658PubMedCrossRefGoogle Scholar
  160. 160.
    Hart R, Norman RJ (2013) The longer-term health outcomes for children born as a result of IVF treatment: part I—general health outcomes. Hum Reprod Update 19(3):232–243PubMedCrossRefGoogle Scholar
  161. 161.
    Marques CJ, Carvalho F, Sousa M, Barros A (2004) Genomic imprinting in disruptive spermatogenesis. Lancet 363(9422):1700–1702PubMedCrossRefGoogle Scholar
  162. 162.
    La Salle S, Trasler JM (2006) Dynamic expression of DNMT3a and DNMT3b isoforms during male germ cell development in the mouse. Dev Biol 296(1):71–82PubMedCrossRefGoogle Scholar
  163. 163.
    Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6(8):597–610PubMedCrossRefGoogle Scholar
  164. 164.
    Goto T, Monk M (1998) Regulation of X-chromosome inactivation in development in mice and humans. Microbiol Mol Biol Rev 62(2):362–378, Pubmed Central PMCID: 98919PubMedPubMedCentralGoogle Scholar
  165. 165.
    Ooi SL, Henikoff S (2007) Germline histone dynamics and epigenetics. Curr Opin Cell Biol 19(3):257–265PubMedCrossRefGoogle Scholar
  166. 166.
    Molaro A, Hodges E, Fang F, Song Q, McCombie WR, Hannon GJ et al (2011) Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 146(6):1029–1041, Pubmed Central PMCID: 3205962PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Oakes CC, Kelly TL, Robaire B, Trasler JM (2007) Adverse effects of 5-aza-2′-deoxycytidine on spermatogenesis include reduced sperm function and selective inhibition of de novo DNA methylation. J Pharmacol Exp Ther 322(3):1171–1180PubMedCrossRefGoogle Scholar
  168. 168.
    Pathak S, Kedia-Mokashi N, Saxena M, D’Souza R, Maitra A, Parte P et al (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(5 Suppl):2253–2263PubMedCrossRefGoogle Scholar
  169. 169.
    Barton TS, Robaire B, Hales BF (2005) Epigenetic programming in the preimplantation rat embryo is disrupted by chronic paternal cyclophosphamide exposure. Proc Natl Acad Sci USA 102(22):7865–7870, Pubmed Central PMCID: 1138259PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Barres R, Zierath JR (2011) DNA methylation in metabolic disorders. Am J Clin Nutr 93(4):897S–900SPubMedCrossRefGoogle Scholar
  171. 171.
    Palmer NO, Fullston T, Mitchell M, Setchell BP, Lane M (2011) SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity. Reprod Fertil Dev 23(7):929–939, Epub 2011/08/30. engPubMedCrossRefGoogle Scholar
  172. 172.
    Farthing CR, Ficz G, Ng RK, Chan CF, Andrews S, Dean W et al (2008) Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet 4(6):e1000116, Pubmed Central PMCID: 2432031PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Jenkins TG, Carrell DT (2012) Dynamic alterations in the paternal epigenetic landscape following fertilization. Front Genet 3:143, Pubmed Central PMCID: 3442791PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Hammoud SS, Low DH, Yi C, Carrell DT, Guccione E, Cairns BR (2014) Chromatin and transcription transitions of mammalian adult germline stem cells and spermatogenesis. Cell stem cell 15(2):239–253PubMedCrossRefGoogle Scholar
  175. 175.
    Dadoune JP (2009) Spermatozoal RNAs: what about their functions? Microsc Res Tech 72(8):536–551PubMedCrossRefGoogle Scholar
  176. 176.
    Lalancette C, Platts AE, Johnson GD, Emery BR, Carrell DT, Krawetz SA (2009) Identification of human sperm transcripts as candidate markers of male fertility. J Mol Med 87(7):735–748PubMedCrossRefGoogle Scholar
  177. 177.
    Felekkis K, Touvana E, Stefanou C, Deltas C (2010) microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia 14(4):236–240, Pubmed Central PMCID: 3031315PubMedPubMedCentralGoogle Scholar
  178. 178.
    Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R (2007) DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet 39(3):380–385, Pubmed Central PMCID: 3008549PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Marczylo EL, Amoako AA, Konje JC, Gant TW, Marczylo TH (2012) Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics 7(5):432–439PubMedCrossRefGoogle Scholar
  180. 180.
    Grandjean V, Gounon P, Wagner N, Martin L, Wagner KD, Bernex F et al (2009) The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development 136(21):3647–3655PubMedCrossRefGoogle Scholar
  181. 181.
    Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441(7092):469–474PubMedCrossRefGoogle Scholar
  182. 182.
    Wagner KD, Wagner N, Ghanbarian H, Grandjean V, Gounon P, Cuzin F et al (2008) RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. Dev Cell 14(6):962–969, Epub 2008/06/10. engPubMedCrossRefGoogle Scholar
  183. 183.
    Gapp K, Soldado-Magraner S, Alvarez-Sanchez M, Bohacek J, Vernaz G, Shu H et al (2014) Early life stress in fathers improves behavioural flexibility in their offspring. Nat Commun 5:5466, Epub 2014/11/19. engPubMedCrossRefGoogle Scholar
  184. 184.
    Ostermeier GC, Miller D, Huntriss JD, Diamond MP, Krawetz SA (2004) Reproductive biology: delivering spermatozoan RNA to the oocyte. Nature 429(6988):154PubMedCrossRefGoogle Scholar
  185. 185.
    Spadafora C (2008) Sperm-mediated ‘reverse’ gene transfer: a role of reverse transcriptase in the generation of new genetic information. Hum Reprod 23(4):735–740PubMedCrossRefGoogle Scholar
  186. 186.
    Ghanayem BI, Bai R, Kissling GE, Travlos G, Hoffler U (2010) Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity. Biol Reprod 82(1):96–104, Pubmed Central PMCID: 2802115, Epub 2009/08/22. engPubMedCrossRefGoogle Scholar
  187. 187.
    Lambrot R, Xu C, Saint-Phar S, Chountalos G, Cohen T, Paquet M et al (2013) Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat Commun 4:2889, Pubmed Central PMCID: 3863903PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Hughes V (2014) Epigenetics: the sins of the father. Nature 507(7490):22–24PubMedCrossRefGoogle Scholar
  189. 189.
    Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA et al (2013) Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 339(6118):448–452, Pubmed Central PMCID: 3847602PubMedCrossRefGoogle Scholar
  190. 190.
    Filkowski JN, Ilnytskyy Y, Tamminga J, Koturbash I, Golubov A, Bagnyukova T et al (2010) Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis 31(6):1110–1115PubMedCrossRefGoogle Scholar
  191. 191.
    Palmer NO, Bakos HW, Owens JA, Setchell BP, Lane M (2012) Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab 302(7):E768–E780, Epub 2012/01/19. engPubMedCrossRefGoogle Scholar

Copyright information

© The American Physiological Society 2016

Authors and Affiliations

  • Tod Fullston
    • 1
    • 2
  • Helana S. Shehadeh
    • 1
  • John E. Schjenken
    • 1
  • Nicole O. McPherson
    • 1
    • 2
  • Sarah A. Robertson
    • 1
  • Deirdre Zander-Fox
    • 1
    • 3
  • Michelle Lane
    • 1
    • 4
  1. 1.Discipline of Obstetrics and Gynaecology, Paediatrics and Reproductive Health, School of Medicine, Robinson Research InstituteUniversity of AdelaideAdelaideAustralia
  2. 2.Freemasons Foundation Centre for Men’s HealthThe University of AdelaideAdelaideAustralia
  3. 3.RepromedDulwichAustralia
  4. 4.Monash IVF GroupMelbourneAustralia

Personalised recommendations