The loss of global DNA methylation due to decreased DNMT expression in the postnatal mouse ovaries may associate with infertility emerging during ovarian aging

Ovarian aging is one of the main causes of female infertility, and its molecular background is still largely unknown. As DNA methylation regulates many oogenesis/folliculogenesis-related genes, the expression levels and cellular localizations of DNA methyltransferases (DNMTs) playing key roles in this process is important in the ovaries from early to aged terms. In the present study, we aimed to evaluate the spatial and temporal expression of the Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l genes as well as global DNA methylation levels in the mouse ovaries during aging. For this purpose, the following groups were created: young (1- and 2-week old; n = 3 from each week), prepubertal (3- and 4-week-old; n = 3 from each week), pubertal (5- and 6-week-old; n = 3 from each week), postpubertal (16- and 18-week-old; n = 3 from each week), and aged (52-, 60- and 72-week-old; n = 3 from each week). We found here that Dnmt1, Dnmt3a, and Dnmt3l genes' expression at mRNA and protein levels as well as global DNA methylation profiles were gradually and significantly decreased in the postnatal ovaries from young to aged groups (P < 0.05). In contrast, there was a remarkable increase of Dnmt3b expression in the pubertal, postpubertal and aged groups (P < 0.05). Our findings suggest that the significantly altered DNMT expression and global DNA methylation levels during ovarian aging may contribute to female infertility development at the later terms of lifespan. Also, new researches are required to determine the molecular biological mechanism(s) that how altered DNMT expression and decreased DNA methylation lead to ovarian aging.