Impairment of Pol β-related DNA base-excision repair leads to ovarian aging in mice.
Impairment of Pol β-related DNA base-excision repair leads to ovarian aging in mice.
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DOI：
10.18632/aging.104123
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发表时间：
2020-11-20
期刊：
影响因子：
--
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Hua K;Wang L;Sun J;Zhou N;Zhang Y;Ji F;Jing L;Yang Y;Xia W;Hu Z;Pan F;Chen X;Yao B;Guo Z
年龄和人类卵泡储备消耗之间的相关机制仍然不确定。许多研究发现DNA聚合酶β（Pol β）介导的DNA碱基切除修复（BER）损伤导致小鼠卵母细胞老化。随着年龄的增长，DNA损伤在原始卵泡中积累。然而，大多数DNA BER基因的表达，包括APE 1，OGG 1，XRCC 1，连接酶I，连接酶α，PCNA和FEN 1，在小鼠卵母细胞老化过程中保持不变。Pol β+/-杂合子小鼠的生殖能力受损，原始卵泡数低于野生型（wt）小鼠。杂合子小鼠DNA损伤增加。此外，Pol β基因敲低导致卵母细胞DNA损伤增加，卵母细胞存活率降低。过表达Pol β的卵母细胞显示衰老细胞的活力显著增强。此外，血清抗苗勒管激素（AMH）浓度表明，Pol β生殖系突变的年轻小鼠的卵巢储备低于野生型小鼠。这些数据表明，Pol β相关的DNA BER效率是控制小鼠卵母细胞老化的主要因素。
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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