遗传 ›› 2023, Vol. 45 ›› Issue (5): 379-394.doi: 10.16288/j.yczz.23-018
收稿日期:
2023-02-02
修回日期:
2023-03-23
出版日期:
2023-05-20
发布日期:
2023-03-29
通讯作者:
林戈
E-mail:csudnn@csu.edu.cn;linggf@hotmail.com
作者简介:
张楠,在读硕士研究生,专业方向:生殖医学。E-mail: 基金资助:
Nan Zhang1(), Jue Zhang2, Ge Lin1,2()
Received:
2023-02-02
Revised:
2023-03-23
Online:
2023-05-20
Published:
2023-03-29
Contact:
Lin Ge
E-mail:csudnn@csu.edu.cn;linggf@hotmail.com
Supported by:
摘要:
DNA损伤是影响配子发生和胚胎发育的关键因素之一。卵母细胞容易被各种内外源因素(如活性氧、辐射、化疗药物等)诱发DNA损伤。目前研究发现,对于各类DNA损伤,各发育阶段的卵母细胞能够做出相应的DNA损伤反应,通过复杂的机制对DNA进行修复或者启动细胞凋亡。相比于进入生长阶段的卵母细胞,原始卵泡卵母细胞更容易被DNA损伤诱导凋亡。DNA损伤不易诱导卵母细胞减数分裂成熟进程停滞,然而携带DNA损伤的卵母细胞的发育能力明显下降。在临床上,衰老、放疗和化疗是导致女性卵母细胞DNA损伤、卵巢储备降低和不孕的常见原因。为此,人们尝试了能够减轻卵母细胞DNA损伤和增强DNA修复能力的多种方法,试图保护卵母细胞。本文对哺乳动物的各发育阶段卵母细胞的DNA损伤与修复的相关研究进行了梳理和总结,并讨论了其潜在的临床价值,以期为生育力保护提供新的策略。
张楠, 张珏, 林戈. 哺乳动物卵母细胞的DNA损伤与修复研究进展[J]. 遗传, 2023, 45(5): 379-394.
Nan Zhang, Jue Zhang, Ge Lin. Advances in the study of DNA damage and repair in mammalian oocytes[J]. Hereditas(Beijing), 2023, 45(5): 379-394.
图1
各发育阶段卵母细胞的DDR与DNA修复机制 生育高龄女性的卵巢储备减少和卵母细胞质量下降是生殖临床中的常见现象。衰老引起卵母细胞DNA损伤积累和DNA修复能力下降,而ROS增多是衰老损伤细胞DNA的主要机制之一。研究表明,褪黑素等抗氧化剂能够有效减轻ROS诱导的DNA DNA损伤发生时,原始卵泡和初级卵泡的卵母细胞均通过TAp63介导的反应发生凋亡。卵母细胞进入生长阶段后,TAp63水平下降,参与MMR、BER、NER、HR和NHEJ等DNA修复途径的基因表达水平增加。HR和NHEJ机制在卵母细胞的DSBs修复中发挥重要作用。在卵母细胞减数分裂成熟期间,DSBs修复途径从HR过渡到NHEJ。对于ICLs和8-OHdG损伤,卵母细胞可分别通过FANCE和BER途径进行修复。卵母细胞的其他类型DNA损伤的修复机制有待验证。卵母细胞缺乏经典的由ATM-CHK1介导的G2/前期DNA损伤检查点,但似乎具有一个由MDC1介导的非经典G2/前期DNA损伤检查点。此外,SAC介导了卵母细胞的MI期停滞反应。"
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