Integrated Analyses of Phenotype and Quantitative Proteome of CMTM4 Deficient Mice Reveal Its Association with Male Fertility.

作者: FuJun Liu , XueXia Liu , Xin Liu , Ting Li , Peng Zhu

DOI: 10.1074/MCP.RA119.001416

关键词: Male infertilityNucleosomal DNA bindingSpermatogenesisAcrosome reactionAcrosomeSpermBiologySperm motilityAndrologyIn vitro fertilisation

摘要: The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene that has been implicated in male reproduction. CMTM4 an evolutionarily conserved member highly expressed the testis. However, its function fertility remains unknown. Here, we demonstrate associated with spermatogenesis and sperm quality. Using Western blotting immunohistochemical analyses, found expression to be decreased poor-quality human spermatozoa, old testes, testicular biopsies nonobstructive azoospermia. CRISPR-Cas9 technology, knocked out Cmtm4 mice. These knockout (KO) mice showed reduced daily production, lower epididymal motility increased proportion of abnormally backward-curved heads bent midpieces. also had evident sub-fertile phenotype, characterized by low pregnancy rates on prolonged breeding wild type female mice, vitro fertilization efficiency percentage acrosome reactions. We then performed quantitative proteomic analysis where identified 139 proteins downregulated Cmtm4-KO 100 (71.9%) which were related reaction. same was sperm, 3588 409 being differentially regulated Our enrichment upregulated enriched nucleosomal DNA binding functions actin functions. findings elucidate roles demonstrates potential as promising molecular candidate for quality assessment diagnosis or treatment infertility.

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