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

作者：Hua, Ke; Wang, Liping; Sun, Junhua; Zhou, Nanhai; Zhang, Yilan; Ji, Feng; Jing, Li; Yang, Yang; Xia, Wen; Hu, Zhigang; Pan, Feiyan; Chen, Xi; Yao, Bing; Guo, Zhigang^*

来源：Aging-US, 2020, 12(24): 25207-25228.

• ovarian aging
• BER
• Pol beta
• menopause
• oocytes

The mechanism underlying the association between age and depletion of the human ovarian follicle reserves remains uncertain. Many identified that impaired DNA polymerase beta (Pol beta)-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 a, PCNA and FEN1, remains unchanged during aging in mouse oocytes. Also, the reproductive capacity of Pol beta+/- 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 beta knockdown leads to increased DNA damage in oocytes and decreased survival rate of oocytes. Oocytes over-expressing Pol beta showed that the vitality of senescent cells enhances significantly. Furthermore, serum concentrations of anti-Mullerian hormone (AMH) indicated that the ovarian reserves of young mice with Pol beta germline mutations were lower than those in wt. These data show that Pol beta-related DNA BER efficiency is a major factor governing oocyte aging in mice.

• 单位
  南京师范大学; 南京大学; 嘉兴学院