Research Paper Volume 12, Issue 24 pp 25207—25228
Impairment of Pol β-related DNA base-excision repair leads to ovarian aging in mice
- 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
- 2 Center of Reproductive Medicine, Jiaxing Maternity and Child Health Care Hospital, College of Medicine, Jiaxing University, Jiaxing 314000, China
- 3 Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Jiangsu 210002, China
- 4 School of Life Sciences, Nanjing University, Nanjing 210093, China
Received: June 22, 2020 Accepted: August 31, 2020 Published: November 20, 2020https://doi.org/10.18632/aging.104123
How to Cite
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.
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.