A Lack of Contact of Sperm with Accessory Sex Gland Secretions Deregulates DNA Methylation and Imprinted Gene Expression in Rodent Embryos

Abstract

Increased oxidative DNA damage is observed in sperm devoid of contact with accessory sex gland (ASG) secretion. After fertilization, these sperm may produce abnormal embryos. In this study, we investigated the possibility that the pattern of DNA methylation and imprinted gene expression in these embryos may be perturbed. Epididymal sperm, uterine sperm, and embryonic day 13 (E13) embryos were collected from hamster and mouse. The extent of global DNA methylation was determined with an antibody against methylcytosine using an embryo DNA dot. The sperm and embryo Gtl2 promoter and H19 differential methylated region (DMR) were subject to bisulfite sequencing. Expression of their reciprocally activated genes Dlk1 and Igf2 was quantified by real-time PCR. Genome-wide DNA hypomethylation in both hamster and mouse embryos sired by males without ASG was observed. The imprinting pattern of fetal mouse Gtl2 promoter and fetal hamster H19 DMR were also disrupted while the expression of Dlk1 and Igf2 was dysregulated in the hamster embryo. This study suggests that a lack of contact of sperm with the ASG secretion disrupts genomewide DNA methylation and also affects the DNA methylation pattern of imprinted genes in embryos.

Paternal diet-induced obesity impairs embryo development and implantation in the mouse

“…Just one study has examined SP in this context, reporting a negative correlation between BMI and SP neutral a-glucosidase levels, suggestive of altered epidiymal function (57). Furthermore, the importance of SP for normal sperm methylation has been described (58). Such molecular changes, including gene transcription and the establishment of epigenetic marks, could also be perturbed as a consequence of the environment or disease states such as obesity.…”

Mysteries and unsolved problems of mammalian fertilization and related topics

“…In these females, fertilization proceeded normally, but many embryos died during their post-implantation development. Later, it was found that seminal plasma protects spermatozoa from oxidative stress [ 283 ], which may alter the DNA methylation pattern of imprinted genes in embryos [ 284 ]. These reports need further confirmation.…”