Abstract
A growing number of sperm methylome analyses have identified genomic loci that are susceptible to paternal age effects in a variety of mammalian species, including human, bovine, and mouse. However, there is little overlap between different data sets. Here, we studied whether or not paternal age effects on the sperm epigenome have been conserved in mammalian evolution and compared methylation patterns of orthologous regulatory regions (mainly gene promoters) containing both conserved and non-conserved CpG sites in 94 human, 36 bovine, and 94 mouse sperm samples, using bisulfite pyrosequencing. We discovered three (NFKB2, RASGEF1C, and RPL6) age-related differentially methylated regions (ageDMRs) in humans, four (CHD7, HDAC11, PAK1, and PTK2B) in bovines, and three (Def6, Nrxn2, and Tbx19) in mice. Remarkably, the identified sperm ageDMRs were all species-specific. Most ageDMRs were in genomic regions with medium methylation levels and large methylation variation. Orthologous regions in species not showing this age effect were either hypermethylated (>80%) or hypomethylated (<20%). In humans and mice, ageDMRs lost methylation, whereas bovine ageDMRs gained methylation with age. Our results are in line with the hypothesis that sperm ageDMRs are in regions under epigenomic evolution and may be part of an epigenetic mechanism(s) for lineage-specific environmental adaptations and provide a solid basis for studies on downstream effects in the genes analyzed here.
Highlights
The sperm epigenome is the end product of male germline reprogramming, which is affected by stochastic and environmental factors, including male infertility, paternal diet, and aging [1,2]
Using bisulfite pyrosequencing in 94 human, 36 bovine, and 94 mouse sperm samples, to screen candidate genes for paternal age effects, we identified a number of age-related differentially methylated regions (ageDMRs) in the human (NFKB2, RASGEF1C, and RPL6), bovine (CHD7, HDAC11, PAK1, and PTK2B), and mouse (Def6, Nrxn2, and Tbx19) sperm epigenomes, respectively
The main finding of this study is that sperm methylation patterns found in geneGene regionsHSA
Summary
The sperm epigenome is the end product of male germline reprogramming, which is affected by stochastic and environmental factors, including male infertility, paternal diet, and aging [1,2]. Accumulating evidence indicates that the sperm methylome affects the embryo development and disease susceptibility of the resulting offspring [4–6]. The increasing rate of de novo genetic mutations in the offspring of older males elevates the risks for some rare monogenic [9] and complex, in particular, neurodevelopmental disorders [10]. The DNA sequence itself, and epigenetic marks must be correctly copied to the daughter cells. Since the error rate of this copying process is estimated to be 10–100 times higher for epigenetic than for genetic information [11], the spermatozoa from older males have accumulated many more epimutations than DNA sequence mutations. In the aging mouse model, sperm DNA methylation changes have been associated with changes in gene methylation and expression in the brain and abnormal behavior in the offspring derived from older males [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
