Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Aging (Albany NY). 2020 May 14;12(10):9686-9713. doi: 10.18632/aging.103237.
Aging is associated with reduced tissue remodeling efficiency and increased fibrosis, characterized by excess collagen accumulation and altered matrix degradation. Ovulation, the process by which an egg is released from the ovary, is one of the most dynamic cycles of tissue wounding and repair. Because the ovary is one of the first organs to age, ovulation and ovarian wound healing is impaired with advanced reproductive age. To test this hypothesis, we induced superovulation in reproductively young and old mice and determined the numbers of eggs ovulated and corpora lutea (CLs), the progesterone producing glands formed post-ovulation. Reproductively old mice ovulated fewer eggs and had fewer CLs relative to young controls. Moreover, reproductively old mice exhibited a greater number of oocytes trapped within CLs and expanded cumulus oocyte complexes within unruptured antral follicles, indicative of failed ovulation. In addition, post-ovulatory tissue remodeling was compromised with age as evidenced by reduced CL vasculature, increased collagen, decreased hyaluronan, decreased cell proliferation and apoptosis, impaired wound healing capacity, and aberrant morphology of the ovarian surface epithelium (OSE). These findings demonstrate that ovulatory dysfunction is an additional mechanism underlying the age-related loss of fertility beyond the reduction of egg quantity and quality.
衰老是与组织重塑效率降低和纤维化增加相关的，其特征是胶原过度积累和基质降解改变。排卵是卵子从卵巢中释放的过程，是组织创伤和修复最具活力的周期之一。由于卵巢是最早衰老的器官之一，因此随着生殖年龄的增长，排卵和卵巢愈合受损。为了验证这一假设，我们在年轻和年老的小鼠中诱导了超排卵，并确定了排卵的卵子数量和黄体（CL），即排卵后形成的孕激素产生腺。与年轻对照组相比，生殖年龄较大的小鼠排卵的卵子较少，黄体较少。此外，生殖年龄较大的小鼠在未破裂的窦卵泡内表现出更多的卵母细胞被困在黄体中，以及扩张的卵丘卵母细胞复合物，表明排卵失败。此外，随着年龄的增长，排卵后的组织重塑受损，表现为 CL 血管减少、胶原增加、透明质酸减少、细胞增殖和凋亡减少、伤口愈合能力受损以及卵巢表面上皮（OSE）形态异常。这些发现表明，排卵功能障碍是除卵子数量和质量下降之外导致与年龄相关的生育力丧失的另一种机制。
