TY  - JOUR
A1  - Prell, Andreas
A1  - Sen, Mustafa Orkun
A1  - Potabattula, Ramya
A1  - Bernhardt, Laura
A1  - Dittrich, Marcus
A1  - Hahn, Thomas
A1  - Schorsch, Martin
A1  - Zacchini, Federica
A1  - Ptak, Grazyna Ewa
A1  - Niemann, Heiner
A1  - Haaf, Thomas
T1  - Species-specific paternal age effects and sperm methylation levels of developmentally important genes
JF  - Cells
N2  - 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.
KW  - age-related differentially methylated regions (ageDMRs)
KW  - bisulfite pyrosequencing
KW  - mammalian male germline
KW  - paternal age effect
KW  - species-specific epigenetic marks
KW  - sperm DNA methylation
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262301
SN  - 2073-4409
VL  - 11
IS  - 4
ER  -