生物钟在卵巢生理和病理中的作用

Roles of the Circadian Clock in Ovarian Physiology and Pathology

哺乳动物的昼夜节律是基因编码的分子钟在体内产生的一种以大约24 h为周期的生理现象,使机体的生理过程与外界环境的变化相协调,是对环境适应的一种表现。在哺乳动物中,繁殖生理功能受生物钟系统的调节。在下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴的各组织中均已观察到生物钟基因的表达,各层次的生物钟相互协调和同步,维持正常的生殖行为。昼夜节律的产生、维持和调控依赖连锁的转录-翻译反馈环路(transcription-translation feedback loop,TTLs),它决定着下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴每个组织中基因表达的周期和振幅。卵巢中生物钟接受下丘脑视交叉上核的神经内分泌调控,但其又具有自主性。环境因素引起的生物钟紊乱会严重损害雌性动物的生殖能力,导致一系列相关的卵巢疾病。另外,生物钟还与卵巢衰老密切相关。基于已有的研究,本文着重阐述卵巢生物钟在卵泡发育、排卵和类固醇生成的作用机制,以及生物钟与卵巢衰老的最新研究进展。还介绍了几种常见的由生物钟紊乱引起的生殖能力下降的卵巢疾病。

The circadian rhythm of mammals is a physiological phenomena that is about 24 hours produced by genetically encoded molecular clocks,making the physiological process of the body coordinated with the changes of the external environment,and it is a manifestation of adaptation to the environment.In mammals,reproductive physiology is regulated by the circadian clock.The expression of circadian clock genes has been observed in each tissue of the hypothalamic-pituitary-ovarian(HPO)axis,and the biological clock at all levels coordinates and synchronizes with each other to maintain normal reproductive behavior.The production,maintenance,and regulation of circadian rhythms depend on a chain of transcription-translation feedback loops(TTLs),which determine the cycle and amplitude of gene expression in each tissue of the HPO axis.The circadian clock of the ovary is regulated by the neuroendocrine regulation of suprachiasmatic nucleus of the hypothalamus,but it is autonomous.Circadian rhythm disruption caused by environmental factors can seriously impair female fertility and lead to a range of related ovarian diseases.In addition,the circadian clock is also closely related to ovarian aging.Based on existing research,this paper focuses on the mechanism of the circadian clock in ovarian follicular development,ovulation and steroid generation,as well as the latest research progress on the relationship between the circadian clock and ovarian aging.In addition,several common ovarian diseases with decreased fertility due to circadian clock disorders are described.