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MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients
Jun-Hao Zhou1, Qi-Zhao Zhou2, Jian-Kun Yang3, Xiao-Ming Lyu4, Jun Bian5, Wen-Bin Guo6, Zi-Jian Chen7, Ming Xia8, Hui Xia9, Tao Qi10, Xin Li11, Cun-Dong Liu12
1 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
Laboratory Medical Center, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
Cancer Research Institute, Southern Medical University, Guangzhou, China
Correspondence Address:
Dr. Cun-Dong Liu
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
Dr. Xin Li
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Cancer Research Institute, Southern Medical University, Guangzhou, China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1008-682X.185001
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Cysteine-rich secretory protein 2 (CRISP2) is an important protein in spermatozoa that plays roles in modulating sperm flagellar motility, the acrosome reaction, and gamete fusion. Spermatozoa lacking CRISP2 exhibit low sperm motility and abnormal morphology. However, the molecular mechanisms underlying the reduction of CRISP2 in asthenoteratozoospermia (ATZ) remain unknown. In this study, low expression of CRISP2 protein rather than its mRNA was observed in the ejaculated spermatozoa from ATZ patients as compared with normozoospermic males. Subsequently, bioinformatic prediction, luciferase reporter assays, and microRNA-27a (miR-27a) transfection experiments revealed that miR-27a specifically targets CRISP2 by binding to its 3' untranslated region (3'-UTR), suppressing CRISP2 expression posttranscriptionally. Further evidence was provided by the clinical observation of high miR-27a expression in ejaculated spermatozoa from ATZ patients and a negative correlation between miR-27a expression and CRISP2 protein expression. Finally, a retrospective follow-up study supported that both high miR-27a expression and low CRISP2 protein expression were associated with low progressive sperm motility, abnormal morphology, and infertility. This study demonstrates a novel mechanism responsible for reduced CRISP2 expression in ATZ, which may offer a potential therapeutic target for treating male infertility, or for male contraception. |
