Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers University Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Reproduction. 2021 Jul 14;162(2):R19-R33. doi: 10.1530/REP-21-0022.
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.
女性的卵巢衰老与卵母细胞数量和质量的逐渐丧失有关。当这些过程发生得较早或加速时，其临床相关表现为卵巢储备功能减退和/或卵巢早衰。这两种情况都会对女性的生殖和整体健康产生重要影响，包括不孕。尽管有许多促成因素，但许多与卵巢衰老相关的过程的分子机制尚未完全阐明。在这篇综述中，我们强调了一些随着年龄增长影响卵母细胞数量和质量的最关键因素。我们讨论了染色体因素，包括着丝粒的恶化和错误分离、减数分裂重组的错误以及纺锤体组装检查点的严格性降低。我们还讨论了与卵巢衰老相关的 DNA 损伤、端粒变化、活性氧和线粒体功能障碍以及与原发性卵巢功能不全和卵巢储备功能减退相关的已知基因突变。此外，还介绍了最近研究发现的与卵巢衰老相关的细胞质因素，包括蛋白质代谢失调和卵巢微环境改变。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，并提出了未来研究的方向。更好地理解卵巢衰老的分子基础最终将导致诊断和治疗的进步，为女性提供有关生殖健康的早期选择的信息。
