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An update on the role and potential mechanisms of clock genes regulating spermatogenesis: A systematic review of human and animal experimental studies

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Abstract

Circadian clocks can be traced in nearly all life kingdoms, with the male reproductive system no exception. However, our understanding of the circadian clock in spermatogenesis seems to fall behind other scenarios. The present review aims to summarize the current knowledge about the role and especially the potential mechanisms of clock genes in spermatogenesis regulation. Accumulating studies have revealed rhythmic oscillation in semen parameters and some physiological events of spermatogenesis. Disturbing the clock gene expression by genetic mutations or environmental changes will also notably damage spermatogenesis. On the other hand, the mechanisms of spermatogenetic regulation by clock genes remain largely unclear. Some recent studies, although not revealing the entire mechanisms, indeed attempted to shed light on this issue. Emerging clues hinted that gonadal hormones, retinoic acid signaling, homologous recombination, and the chromatoid body might be involved in the regulation of spermatogenesis by clock genes. Then we highlight the challenges and the promising directions for future studies so as to stimulate attention to this critical field which has not gained adequate concern.

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Abbreviations

LD cycle:

Light dark cycle

SCN:

Suprachiasmatic nucleus

TTFLs:

Transcriptional–translational feedback loops

HPT axis:

Hypothalamic-pituitary–testicular axis

GnRH:

Gonadotropin-releasing hormone

GnIH:

Gonadotropin-inhibitory hormone

FSH:

Follicle-stimulating hormone

LH:

Luteinizing hormone

hCG:

Human chorionic gonadotropin

BPA:

Bisphenol A

RARα:

Retinoic acid receptors α

RXRα:

Retinoid X receptors

RORα/β/γ:

Retinoic acid-related orphan receptors α/β/γ

REV-ERBα:

Nuclear receptor subfamily 1 group D α

ATAC:

Assay for transposase accessible chromatin with high-throughput sequencing

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Acknowledgements

We thank Siwen Luo for the careful revision of this review.

Funding

This work was supported by the National Key R&D Program of China under Grant [2022YFC2702900], National Natural Science Foundation of China under Grant [81871208], Key Program of National Natural Science Foundation of China under Grant [82130097], and Army Medical University Research Program under Grant [2021XZL01].

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  1. Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China

    Mengchao He, Jia Cao & Qing Chen

  2. Center for Disease Control and Prevention of Southern Theatre Command, Guangzhou, 510630, China

    Kun Liu

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  1. Mengchao He
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M.C.H. and K.L. designed the review, conducted the literature research, and drafted the paper. Q.C. and J.C. designed the review, revised the content critically, and approved the final draft.

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Correspondence to Jia Cao or Qing Chen.

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He, M., Liu, K., Cao, J. et al. An update on the role and potential mechanisms of clock genes regulating spermatogenesis: A systematic review of human and animal experimental studies. Rev Endocr Metab Disord 24, 585–610 (2023). https://doi.org/10.1007/s11154-022-09783-0

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