Ribosomal DNA methylation in human and mouse oocytes increases with age

An age-dependent increase in ribosomal DNA (rDNA) methylation has been observed across a broad spectrum of somatic tissues and the male mammalian germline. Bisulfite pyrosequencing (BPS) was used to determine the methylation levels of the rDNA core promoter and the rDNA upstream control element (UCE) along with two oppositely genomically imprinted control genes (PEG3 and GTL2) in individual human germinal vesicle (GV) oocytes from 90 consenting women undergoing fertility treatment because of male infertility. Apart from a few (4%) oocytes with single imprinting defects (in either PEG3 or GTL2), the analyzed GV oocytes displayed correct imprinting patterns. In 95 GV oocytes from 42 younger women (26-32 years), the mean methylation levels of the rDNA core promoter and UCE were 7.4 +/- 4.0% and 9.3 +/- 6.1%, respectively. In 79 GV oocytes from 48 older women (33-39 years), methylation levels increased to 9.3 +/- 5.3% (P = 0.014) and 11.6 +/- 7.4% (P = 0.039), respectively. An age-related increase in oocyte rDNA methylation was also observed in 123 mouse GV oocytes from 29 4-16-months-old animals. Similar to the continuously mitotically dividing male germline, ovarian aging is associated with a gain of rDNA methylation in meiotically arrested oocytes. Oocytes from the same woman can exhibit varying rDNA methylation levels and, by extrapolation, different epigenetic ages.

Automated summary

An age-dependent increase in rDNA methylation was observed in oocytes from women with male infertility undergoing fertility treatment. The methylation levels of rDNA core promoter and UCE increased with age in both human and mouse oocytes. Variability in rDNA methylation levels suggests different epigenetic ages within oocytes from the same woman.