Winship Amy L, Stringer Jessica M, Liew Seng H, Hutt Karla J
Ovarian Biology Laboratory, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC 3800, Australia.
Hum Reprod Update. 2018 Mar 1;24(2):119-134. doi: 10.1093/humupd/dmy002.
Within the ovary, oocytes are stored in long-lived structures called primordial follicles, each comprising a meiotically arrested oocyte, surrounded by somatic granulosa cells. It is essential that their genetic integrity is maintained throughout life to ensure that high quality oocytes are available for ovulation. Of all the possible types of DNA damage, DNA double-strand breaks (DSBs) are considered to be the most severe. Recent studies have shown that DNA DSBs can accumulate in oocytes in primordial follicles during reproductive ageing, and are readily induced by exogenous factors such as γ-irradiation, chemotherapy and environmental toxicants. DSBs can induce oocyte death or, alternatively, activate a program of DNA repair in order to restore genetic integrity and promote survival. The repair of DSBs has been intensively studied in the context of meiotic recombination, and in recent years more detail is becoming available regarding the repair capabilities of primordial follicle oocytes.
This review discusses the induction and repair of DNA DSBs in primordial follicle oocytes.
PubMed (Medline) and Google Scholar searches were performed using the key words: primordial follicle oocyte, DNA repair, double-strand break, DNA damage, chemotherapy, radiotherapy, ageing, environmental toxicant. The literature was restricted to papers in the English language and limited to reports in animals and humans dated from 1964 until 2017. The references within these articles were also manually searched.
Recent experiments in animal models and humans have provided compelling evidence that primordial follicle oocytes can efficiently repair DNA DSBs arising from diverse origins, but this capacity may decline with increasing age.
Primordial follicle oocytes are vulnerable to DNA DSBs emanating from endogenous and exogenous sources. The ability to repair this damage is essential for female fertility. In the long term, augmenting DNA repair in primordial follicle oocytes has implications for the development of novel fertility preservation agents for female cancer patients and for the management of maternal ageing. However, further work is required to fully characterize the specific proteins involved and to develop strategies to bolster their activity.
在卵巢内，卵母细胞储存在称为原始卵泡的长寿结构中，每个原始卵泡都包含一个减数分裂停滞的卵母细胞，周围环绕着体细胞颗粒细胞。在整个生命过程中维持其遗传完整性至关重要，以确保有高质量的卵母细胞可供排卵。在所有可能的DNA损伤类型中，DNA双链断裂（DSB）被认为是最严重的。最近的研究表明，在生殖衰老过程中，DNA DSB会在原始卵泡的卵母细胞中积累，并且很容易被γ射线照射、化疗和环境毒物等外源性因素诱导产生。DSB可诱导卵母细胞死亡，或者激活DNA修复程序以恢复遗传完整性并促进存活。在减数分裂重组的背景下，对DSB的修复进行了深入研究，近年来，关于原始卵泡卵母细胞的修复能力有了更多详细信息。
本综述讨论原始卵泡卵母细胞中DNA DSB的诱导和修复。
使用关键词“原始卵泡卵母细胞、DNA修复、双链断裂、DNA损伤、化疗、放疗、衰老、环境毒物”在PubMed（Medline）和谷歌学术上进行搜索。文献仅限于英文论文，且限于1964年至2017年的动物和人类报告。还手动搜索了这些文章中的参考文献。
最近在动物模型和人类中的实验提供了令人信服的证据，即原始卵泡卵母细胞可以有效修复源自多种来源的DNA DSB，但这种能力可能会随着年龄的增长而下降。
原始卵泡卵母细胞易受内源性和外源性来源的DNA DSB影响。修复这种损伤的能力对女性生育能力至关重要。从长远来看，增强原始卵泡卵母细胞中的DNA修复对开发针对女性癌症患者的新型生育力保存剂以及对母体衰老的管理具有重要意义。然而，需要进一步的工作来全面表征所涉及的特定蛋白质，并制定增强其活性的策略。
