MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients  

作　　者：Jun-Hao Zhou Qi-Zhao Zhou Jian-Kun Yang Xiao-Ming Lyu Jun Bian Wen-Bin Guo Zi-Jian Chen Ming Xia Hui Xia Tao Qi Xin Li Cun-Dong Liu 

机构地区：[1]Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China [2]Laboratory Medical Center, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China [3]Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China [4]Cancer Research Institute, Southern Medical University, Guangzhou, China

出　　处：《Asian Journal of Andrology》2017年第5期591-595,共5页亚洲男性学杂志（英文版）

基　　金：The authors would like to thank Prof. Chunyan Wang, for her contributions to the samples collection, as well as thank Cheng Yang for his contributions to the figures revision. This study was supported by the Guangdong Provincial Natural Science Foundation of China （No. 2014A030313291, No. 2015A030310027 and No. 2016A030310393）, the Guangdong Provincial Science and Technology Program （No. 2014A020212204）, and the Science and Technology Innovation Project of Southern Medical University （QD2014N005）.

摘　　要：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.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.

关 键 词：asthenoteratozoospermia cysteine-rich secretory protein 2 male infertility microRNA-27a 

分 类 号：Q517[生物学—生物化学] S852.618[农业科学—基础兽医学]