The Sperm Epigenome, Male Aging, and Potential Effects on the Embryo

Jenkins, Timothy G.; Aston, Kenneth I.; Meyer, Tyson D.; Carrell, Douglas T.

doi:10.1007/978-3-319-18881-2_4

Cited by 22 publications

(21 citation statements)

References 54 publications

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“…These findings are consistent with the view that sperm epigenetic marks can transmit paternal effects into the next generation, influencing the offspring’s disease susceptibility (21). Recently, Jenkins et al .…”

Section: Introductionsupporting

confidence: 91%

Paternal age effects on spermFOXK1andKCNA7methylation and transmission into the next generation

Atsem¹,

Reichenbach²,

Potabattula³

et al. 2016

Hum. Mol. Genet.

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Children of older fathers carry an increased risk for developing autism and other disorders. To elucidate the underlying mechanisms, we investigated the correlation of sperm DNA methylation with paternal age and its impact on the epigenome of the offspring. Methylation levels of nine candidate genes and LINE-1 repeats were quantified by bisulfite pyrosequencing in sperm DNA of 162 donors and 191 cord blood samples of resulting children (conceived by IVF/ICSI with the same sperm samples). Four genes showed a significant negative correlation between sperm methylation and paternal age. For FOXK1 and KCNA7, the age effect on the sperm epigenome was replicated in an independent cohort of 188 sperm samples. For FOXK1, paternal age also significantly correlated with foetal cord blood (FCB) methylation. Deep bisulfite sequencing and allele-specific pyrosequencing allowed us to distinguish between maternal and paternal alleles in FCB samples with an informative SNP. FCB methylation of the paternal FOXK1 allele was negatively correlated with paternal age, whereas maternal allele was unaffected by maternal age. Since FOXK1 duplication has been associated with autism, we studied blood FOXK1 methylation in 74 children with autism and 41 age-matched controls. The FOXK1 promoter showed a trend for accelerated demethylation in the autism group. Dual luciferase reporter assay revealed that FOXK1 methylation influences gene expression. Collectively, our study demonstrates that age-related DNA methylation changes in sperm can be transmitted to the next generation and may contribute to the increased disease risk in offspring of older fathers.

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Section: Introductionsupporting

confidence: 91%

Paternal age effects on spermFOXK1andKCNA7methylation and transmission into the next generation

Atsem¹,

Reichenbach²,

Potabattula³

et al. 2016

Hum. Mol. Genet.

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show abstract

Section: Introductionmentioning

confidence: 99%

Intergenerational effects on offspring telomere length: interactions among maternal age, stress exposure and offspring sex

et al. 2019

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Offspring produced by older parents often have reduced longevity, termed the Lansing effect. Because adults usually have similar-aged mates, it is difficult to separate effects of maternal and paternal age, and environmental circumstances are also likely to influence offspring outcomes. The mechanisms underlying the Lansing effect are poorly understood. Variation in telomere length and loss, particularly in early life, is linked to longevity in many vertebrates, and therefore changes in offspring telomere dynamics could be very important in this context. We examined the effect of maternal age and environment on offspring telomere length in zebra finches. We kept mothers under either control (ad libitum food) or more challenging (unpredictable food) circumstances and experimentally minimized paternal age and mate choice effects. Irrespective of the maternal environment, there was a substantial negative effect of maternal age on offspring telomere length, evident in longitudinal and cross-sectional comparisons (average of 39% shorter). Furthermore, in young mothers, sons reared by challenged mothers had significantly shorter telomere lengths than sons reared by control mothers. This effect disappeared when the mothers were old, and was absent in daughters. These findings highlight the importance of telomere dynamics as inter-generational mediators of the evolutionary processes determining optimal age-specific reproductive effort and sex allocation.

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“…Compared to women, the decline in male reproductive capacity with age is less pronounced and men are considered to be able to have a child throughout their lifespan. In literature, the role and the importance of maternal age in fertilization has been extensively studied; however, the effect of the paternal age is poorly understood [1][2][3][4][5]. Now, especially in developed countries, the fact that couples postpone having a child due to economic reasons, high standards of living, or career planning has substantially increased the significance of research for investigating the effects of aging on reproductive systems [1].…”

Section: Introductionmentioning

confidence: 99%

Effects of aging on the male reproductive system

Güneş

Hekim

Arslan

et al. 2016

J Assist Reprod Genet

190

118

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The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitarygonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

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The Sperm Epigenome, Male Aging, and Potential Effects on the Embryo

Cited by 22 publications

References 54 publications

Paternal age effects on spermFOXK1andKCNA7methylation and transmission into the next generation

Paternal age effects on spermFOXK1andKCNA7methylation and transmission into the next generation

Intergenerational effects on offspring telomere length: interactions among maternal age, stress exposure and offspring sex

Effects of aging on the male reproductive system

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