Aging-Induced Changes in Sperm DNA Methylation are Modified by Low Dose of Perinatal Flame Retardants
J. Richard Pilsner, Alex Shershebnev, Haotian Wu, Chelsea Marcho, О. П. Дрибноходова, Victoria Shtratnikova, Oleg Sergeyev, Alexander Suvorov
Abstract
Aims: Paternal age is increasing in developed countries. Understanding of aging-related epigenetic changes in sperm is needed as well as factors that modify such changes. Materials & methods: Young pubertal and mature rats were exposed perinatally to vehicle or environmental xenobiotic 2,2′,4,4′-tetrabromodiphenyl ether. Epididymal sperm was reduced representation bisulfite sequenced. Differentially methylated regions (DMRs) were identified via MethPipe. Results: In control animals, 5319 age-dependent DMRs were identified. Age-related DMRs were enriched for embryonic development. In exposed rats, DNA methylation was higher in young and lower in mature animals then in controls. Conclusions: Sperm methylome undergoes significant age-dependent changes, which may represent a causal link between paternal age and offspring phenotype. Environmental xenobiotics can interfere with the natural process of epigenetic aging.