Mechanisms of ovarian aging.
Mechanisms of ovarian aging.
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DOI：
10.1530/rep-21-0022
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发表时间：
2021-07-14
期刊：
影响因子：
3.8
通讯作者：
Berkowitz, Karen M.
中科院分区：
文献类型：
--
作者：
Park, Selena U.;Walsh, Leann;Berkowitz, Karen M.
女性卵巢老化与卵母细胞数量和质量的逐渐丧失相关。当这些过程发生早或加速时，其临床相关性是卵巢储备减少和/或卵巢功能不全。这两种情况对妇女的生殖健康和一般健康，包括不孕症，都有重要影响。虽然有许多促成因素，但与卵巢衰老相关的许多过程的分子机制尚未完全阐明。在这篇综述中，我们强调了一些最关键的因素，影响卵母细胞的数量和质量随着年龄的增长。我们讨论了染色体因素，包括凝聚力恶化和错误分离，减数分裂重组的错误，并降低严格的纺锤体组装检查点。DNA损伤，端粒的变化，活性氧和线粒体功能障碍，因为它们与卵巢衰老，以及众所周知的基因突变与原发性卵巢功能不全和卵巢储备减少也进行了讨论。此外，研究调查最近承认的细胞质因素与卵巢衰老，包括蛋白质代谢失调和卵巢微环境的改变。我们使用小鼠和人类研究来支持这些因素在生理和加速卵巢衰老中的作用，并为未来的研究提出了方向。更好地了解卵巢衰老的分子基础将最终导致诊断和治疗的进步，为妇女提供信息，使其更早地选择生殖健康。
Ovarian aging in women correlates with the progressive loss of both the number and quality of oocytes. When these processes occur early or are accelerated, their clinical correlates are diminished ovarian reserve and/or premature ovarian insufficiency. Both these conditions have important consequences for the reproductive and general health of women, including infertility. Although there are many contributing factors, the molecular mechanisms underlying many of the processes associated with ovarian aging have not been fully elucidated. In this review, we highlight some of the most critical factors that impact oocyte quantity and quality with advancing age. We discuss chromosomal factors including cohesion deterioration and mis-segregation, errors in meiotic recombination, and decreased stringency of the spindle assembly checkpoint. DNA damage, telomere changes, reactive oxygen species and mitochondrial dysfunction as they relate to ovarian aging, and well-known gene mutations associated with primary ovarian insufficiency and diminished ovarian reserve are also discussed. Additionally, studies investigating recently acknowledged cytoplasmic factors associated with ovarian aging including protein metabolic dysregulation and microenvironmental alterations in the ovary are presented. We use both mouse and human studies to support the roles these factors play in physiologic and expedited ovarian aging, and we propose directions for future studies. A better understanding of the molecular basis of ovarian aging will ultimately lead to diagnostic and therapeutic advancements that would provide women with information to make earlier choices about their reproductive health.