Age-Associated Sperm DNA Methylation Alterations: Possible Implications in Offspring Disease Susceptibility

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There is a striking trend of delayed parenthood in developed countries due to secular and socioeconomic pressures. As a result, physicians commonly consult with concerned patients inquiring about the impact of advanced age on their ability to conceive healthy offspring. The concern has more frequently surrounded the effects of advanced maternal age, but recent evidence suggests negative effects of advanced paternal age as well. Specifically, studies have demonstrated increased incidence of neuropsychiatric and other disorders in the offspring of older males. In this study we have investigated a commonly hypothesized mechanism for this effect, namely sperm DNA methylation alteration. Our data indicate that specific genomic regions of DNA methylation are commonly altered with age, suggesting that some regions of the sperm genome are more susceptible than others to age-related epigenetic changes. Importantly, a significant portion of these alterations occur at genes known to be associated with schizophrenia and bipolar disorder, both of which display increased incidence in the offspring of older fathers. These data will be important in driving future studies aimed at determining the impact that these methylation alterations may have on offspring health and will thus enable couples at advanced reproductive ages to be more informed of possible risks.

Vyšlo v časopise: Age-Associated Sperm DNA Methylation Alterations: Possible Implications in Offspring Disease Susceptibility. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004458
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004458

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1. HareEH, MoranPA (1979) Raised parental age in psychiatric patients: evidence for the constitutional hypothesis. Br J Psychiatry 134: 169–177.

2. MillerB, MessiasE, MiettunenJ, AlaraisanenA, JarvelinMR, et al. (2011) Meta-analysis of paternal age and schizophrenia risk in male versus female offspring. Schizophr Bull 37: 1039–1047.

3. FransEM, SandinS, ReichenbergA, LichtensteinP, LangstromN, et al. (2008) Advancing paternal age and bipolar disorder. Arch Gen Psychiatry 65: 1034–1040.

4. GoldbergYP, KremerB, AndrewSE, TheilmannJ, GrahamRK, et al. (1993) Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nat Genet 5: 174–179.

5. AndrewSE, GoldbergYP, KremerB, TeleniusH, TheilmannJ, et al. (1993) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 4: 398–403.

6. BrunnerHG, BruggenwirthHT, NillesenW, JansenG, HamelBC, et al. (1993) Influence of sex of the transmitting parent as well as of parental allele size on the CTG expansion in myotonic dystrophy (DM). Am J Hum Genet 53: 1016–1023.

7. ZhengCJ, ByersB, MoolgavkarSH (1993) Allelic instability in mitosis: a unified model for dominant disorders. Proc Natl Acad Sci U S A 90: 10178–10182.

8. OksuzyanS, CrespiCM, CockburnM, MezeiG, KheifetsL (2012) Birth weight and other perinatal characteristics and childhood leukemia in California. Cancer Epidemiol 36: e359–365.

9. MurrayL, McCarronP, BailieK, MiddletonR, Davey SmithG, et al. (2002) Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study. Br J Cancer 86: 356–361.

10. HemminkiK, KyyronenP, VaittinenP (1999) Parental age as a risk factor of childhood leukemia and brain cancer in offspring. Epidemiology 10: 271–275.

11. YipBH, PawitanY, CzeneK (2006) Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol 35: 1495–1503.

12. HammoudSS, NixDA, ZhangH, PurwarJ, CarrellDT, et al. (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460: 473–478.

13. ErkekS, HisanoM, LiangCY, GillM, MurrR, et al. (2013) Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat Struct Mol Biol 20: 868–875.

14. ArpanahiA, BrinkworthM, IlesD, KrawetzSA, ParadowskaA, et al. (2009) Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res 19: 1338–1349.

15. KaatiG, BygrenLO, PembreyM, SjostromM (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15: 784–790.

16. PembreyME, BygrenLO, KaatiG, EdvinssonS, NorthstoneK, et al. (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14: 159–166.

17. CaroneBR, FauquierL, HabibN, SheaJM, HartCE, et al. (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143: 1084–1096.

18. ChristensenBC, HousemanEA, MarsitCJ, ZhengS, WrenschMR, et al. (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5: e1000602.

19. DayK, WaiteLL, Thalacker-MercerA, WestA, BammanMM, et al. (2013) Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol 14: R102.

20. HorvathS (2013) DNA methylation age of human tissues and cell types. Genome Biol 14: R115.

21. RichardsonB (2003) Impact of aging on DNA methylation. Ageing Res Rev 2: 245–261.

22. ThompsonRF, AtzmonG, GheorgheC, LiangHQ, LowesC, et al. (2010) Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9: 506–518.

23. KreimerU, SchulzWA, KochA, NiegischG, GoeringW (2013) HERV-K and LINE-1 DNA Methylation and Reexpression in Urothelial Carcinoma. Front Oncol 3: 255.

24. DerooLA, BolickSC, XuZ, UmbachDM, ShoreD, et al. (2013) Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study. Carcinogenesis 35: 333–338.

25. JenkinsTG, AstonKI, CairnsBR, CarrellDT (2013) Paternal aging and associated intraindividual alterations of global sperm 5-methylcytosine and 5-hydroxymethylcytosine levels. Fertil Steril 4: 945–951.

26. UnrynBM, CookLS, RiabowolKT (2005) Paternal age is positively linked to telomere length of children. Aging Cell 4: 97–101.

27. NjajouOT, CawthonRM, DamcottCM, WuSH, OttS, et al. (2007) Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A 104: 12135–12139.

28. AllsoppRC, VaziriH, PattersonC, GoldsteinS, YounglaiEV, et al. (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A 89: 10114–10118.

29. GorielyA, WilkieAO (2012) Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. Am J Hum Genet 90: 175–200.

30. PaulC, RobaireB (2013) Ageing of the male germ line. Nat Rev Urol 10: 227–234.

31. SerrettiA, MandelliL (2008) The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions. Mol Psychiatry 13: 742–771.

32. LungFW, TzengDS, ShuBC (2002) Ethnic heterogeneity in allele variation in the DRD4 gene in schizophrenia. Schizophr Res 57: 239–245.

33. WeiJ, HemmingsGP (2004) TNXB locus may be a candidate gene predisposing to schizophrenia. Am J Med Genet B Neuropsychiatr Genet 125B: 43–49.

34. TochigiM, ZhangX, OhashiJ, HibinoH, OtowaT, et al. (2007) Association study between the TNXB locus and schizophrenia in a Japanese population. Am J Med Genet B Neuropsychiatr Genet 144B: 305–309.

35. GorbunovaV, SeluanovA, MittelmanD, WilsonJH (2004) Genome-wide demethylation destabilizes CTG.CAG trinucleotide repeats in mammalian cells. Hum Mol Genet 13: 2979–2989.

36. NanassyL, CarrellDT (2011) Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination. Asian J Androl 13: 342–346.

37. BoissonnasCC, AbdalaouiHE, HaelewynV, FauqueP, DupontJM, et al. (2010) Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men. Eur J Hum Genet 18: 73–80.