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男(雄)性生殖系统节律性与非节律性功能调控及生殖损害：生物钟基因的作用和机制研究进展

何孟超, 代应忠, 王艺蒙, 李沁儒, 罗斯文, 凌曦, 王童, 曹佳, 陈卿^*

陆军军医大学(第三军医大学)军事预防医学系毒理学研究所，电磁辐射与医学防护教育部重点实验室，创伤与化学中毒全国重点实验室，重庆 400038

摘要

近年来，男性生殖健康问题受到广泛关注，其中昼夜节律紊乱对男性的生殖损害效应逐渐被认可。然而其通过干扰生物钟系统导致男性生殖损害的机制尚不明确。本文首先总结了生物钟基因对男(雄)性生殖系统的双重调控作用：一方面通过节律性调控下丘脑-垂体-睾丸(hypothalamic-pituitary-testicular axis, HPT)轴和下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenalaxis, HPA)轴参与睾酮合成过程，另一方面通过非节律性机制直接调控精子发生过程。本文进一步梳理了昼夜节律紊乱损害男(雄)性生育力的可能机制，包括通过干扰生殖系统节律功能，即HPT轴同步化、HPT轴与HPA轴相互作用，以及通过干扰生殖系统非节律功能直接导致生精细胞损伤。未来，时空组学技术、表观遗传组学检测、神经环路示踪技术等在男性生殖系统研究中的应用可能为系统揭示昼夜节律紊乱通过生物钟基因导致男性生殖损伤的机制提供新的线索。

关键词： 昼夜节律紊乱; 生物钟; 男性生殖; 下丘脑-垂体-睾丸轴; 下丘脑-垂体-肾上腺轴; 精子发生

Circadian and non-circadian regulation of the male reproductive system and reproductive damage: advances in the role and mechanisms of clock genes

HE Meng-Chao, DAI Ying-Zhong, WANG Yi-Meng, LI Qin-Ru, LUO Si-Wen, LING Xi, WANG Tong, CAO Jia, CHEN Qing^*

State Key Laboratory of Trauma and Chemical Poisoning, Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China

Abstract

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.

Key words: circadian disruption; circadian clock; male fertility; hypothalamic-pituitary-testicular axis; hypothalamic-pituitaryadrenal axis; spermatogenesis

收稿日期：　　录用日期：

通讯作者：陈卿　　E-mail:

DOI: 10.13294/j.aps.2025.0060

引用本文：

何孟超, 代应忠, 王艺蒙, 李沁儒, 罗斯文, 凌曦, 王童, 曹佳, 陈卿. 男(雄)性生殖系统节律性与非节律性功能调控及生殖损害：生物钟基因的作用和机制研究进展[J]. 生理学报 2025; 77 (4): 712-720.

HE Meng-Chao, DAI Ying-Zhong, WANG Yi-Meng, LI Qin-Ru, LUO Si-Wen, LING Xi, WANG Tong, CAO Jia, CHEN Qing. Circadian and non-circadian regulation of the male reproductive system and reproductive damage: advances in the role and mechanisms of clock genes. Acta Physiol Sin 2025; 77 (4): 712-720 (in Chinese with English abstract).