title: MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients.
abstract: 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.
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Jun-Hao
authors: JH
authors: Zhou
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Qi-Zhao
authors: QZ
authors: Zhou
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Jian-Kun
authors: JK
authors: Yang
authors: Laboratory Medical Center, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Xiao-Ming
authors: XM
authors: Lyu
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Jun
authors: J
authors: Bian
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Wen-Bin
authors: WB
authors: Guo
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Zi-Jian
authors: ZJ
authors: Chen
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Ming
authors: M
authors: Xia
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Hui
authors: H
authors: Xia
authors: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Tao
authors: T
authors: Qi
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.|Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Xin
authors: X
authors: Li
authors: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors: Cun-Dong
authors: CD
authors: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D053627:Asthenozoospermia / Q000235:genetics*; D015815:Cell Adhesion Molecules; D019295:Computational Biology; D005500:Follow-Up Studies; D018390:Gene Targeting; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012189:Retrospective Studies; D013081:Sperm Motility / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D020413:3' Untranslated Regions; C062621:CRISP2 protein, human; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs