哺乳动物卵母细胞的DNA损伤与修复研究进展

Advances in the study of DNA damage and repair in mammalian oocytes

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。

DNA damage is one of the key factors affecting gametogenesis and embryo development.Oocytes are susceptible to DNA damage induced by various endogenous and exogenous factors(e.g.,reactive oxygen species,radiation,chemotherapeutic agents,etc.).Current research has revealed that oocytes at various developmental stages are able to respond to various types of DNA damage,repairing DNA or initiating apoptosis through complex mechanisms.Primordial follicular oocytes are more susceptible to apoptosis induced by DNA damage than oocytes entering the growth stage.DNA damage is less likely to induce arrest of the meiotic maturation process in oocytes,however the developmental capacity of oocytes carrying DNA damage is significantly reduced.In clinical practice,aging,radiation and chemotherapy are common causes of oocyte DNA damage,reduced ovarian reserve and infertility in women.Therefore,various methods that can reduce DNA damage and enhance DNA repair in oocytes have been tried in an attempt to protect oocytes.In this review,we systematically summarize the mechanisms of DNA damage and repair in mammalian oocytes at various developmental stages and discuss their potential clinical value with the aim to provide new strategies for fertility protection.