Impairment of Pol β-related DNA base-excision repair leads to ovarian aging in mice.

Aging
Ke HuaZhigang Guo

Abstract

The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. Many identified that impaired DNA polymerase β (Pol β)-mediated DNA base-excision repair (BER) drives to mouse oocyte aging. With aging, DNA lesions accumulate in primordial follicles. However, the expression of most DNA BER genes, including APE1, OGG1, XRCC1, Ligase I, Ligase α, PCNA and FEN1, remains unchanged during aging in mouse 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 enhances 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.

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BETA
PCR
electrophoresis
ELISA
X-ray
transgenic
genotyping
biopsies

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