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Altered circadian clock gene expression in the sperm of infertile men with asthenozoospermia



Male infertility is a complex multifactorial pathological condition, and asthenozoospermia (AZS) is one of the most common causes. Current evidence suggests the underlying role of the circadian clock on male fertility. This study aims to evaluate the expression levels of five principal clock genes in the sperm and their correlations with the sperm parameters in male infertility.


We determined the expression profiles of BMAL1, CLOCK, CRY1, PER1, and PER2 in the sperm of infertile men with AZS (n=38) and healthy fertile men (n=40) using quantitative real-time PCR. Then we performed comprehensive association analyses on the clock gene levels and the sperm parameters, including progressive and total motility, concentration, and normal morphology of the sperm.


Our results showed that the expression levels of five clock genes (BMAL1, CLOCK, CRY1, PER1, and PER2) are significantly decreased in the sperm of the infertile men with AZS as compared with that of healthy fertile men (P< 0.01). All five clock gene levels are associated with the percentage of progressive/total sperm motility (r= 0.546/0.589~0.677/0.695, P< 0.01). We also discovered that a combination of BMAL1, CLOCK, CRY1, PER1, and PER2 could reach a high diagnostic performance (areas under the curves, 92%) for infertility with AZS.


This study first reports that sperm BMAL1, CLOCK, CRY1, PER1, and PER2 levels are altered in AZS and may be molecular markers for male infertility with AZS. These findings indicate the possibility of stabilizing circadian rhythmicity through therapeutic intervention on clock genes to prevent and treat infertility.

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Authors and Affiliations



PZ and YL designed the project of this manuscript, and PZ and CL carried out all the experiments. PZ and YG contributed to statistical analyses and results interpretation. PZ and YL contributed to the drafting of the manuscript. YL revised the paper. All authors edited and approved the final version of the manuscript.

Corresponding author

Correspondence to Yifu Leng.

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This study has been granted ethical approval by the Ethics Committee of The Affiliated Zhongshan Hospital of Dalian University (approval number: 2019326).

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The authors declare no competing interests.

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Zhang, P., Li, C., Gao, Y. et al. Altered circadian clock gene expression in the sperm of infertile men with asthenozoospermia. J Assist Reprod Genet 39, 165–172 (2022).

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  • Male infertility
  • Asthenozoospermia
  • Sperm
  • Clock gene
  • Circadian rhythm