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Research Paper|Volume 12, Issue 24|pp 25207—25228

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

Ke Hua1,2, Liping Wang2, Junhua Sun1, Nanhai Zhou1, Yilan Zhang1, Feng Ji1, Li Jing1, Yang Yang1, Wen Xia1, Zhigang Hu1, Feiyan Pan1, Xi Chen4, Bing Yao3, Zhigang Guo1
  • 1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
  • 2Center of Reproductive Medicine, Jiaxing Maternity and Child Health Care Hospital, College of Medicine, Jiaxing University, Jiaxing 314000, China
  • 3Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Jiangsu 210002, China
  • 4School of Life Sciences, Nanjing University, Nanjing 210093, China
* Equal contribution
Received: June 22, 2020Accepted: August 31, 2020Published: November 20, 2020

Copyright: © 2020 Hua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.