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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

Received: 　　Accepted:

Corresponding author: 陈卿　　E-mail:

DOI: 10.13294/j.aps.2025.0060

Citing This Article：

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).