The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. With aging, DNA lesions accumulate in primordial follicles. At the same time, the expression of DNA polymerase β (Pol β) in the oocytes decreased, unable to correct the base mutation on the DNA, leading to irreversible apoptosis of the oocytes. For the first time, Guo’s lab identified that impaired Pol β -mediated DNA base-excision repair (BER) drives to mouse oocyte aging. Pol β was found to be essential for maintaining genomic stability in oocytes. Also, the reproductive capacity of Pol β+/- heterozygote mice was impaired, and the primordial follicle counts were lower than that of wild type (wt) mice. The DNA lesions of heterozygous mice increased. Moreover, the Pol β knockdown leads to increased DNA damage in oocytes and decreased survival rate of oocytes. Oocytes over-expressing Pol β showed that the vitality of senescent cells enhancesis significantly. Furthermore, serum concentrations of anti-Müllerian hormone (AMH) indicated that the ovarian reserves of young mice with Pol β germline mutations were lower than those in wt. These data show that Pol β-related DNA BER efficiency is a major factor governing oocyte aging in mice.

The research with the topic of "Impairment of Pol β -related DNA Base-excision repair leads to ovarian aging in mice" has been published online in the journal of Aging-US. (URL: www.aging-us.com/article/104123)