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

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

SUBMITTER: Liu F

PROVIDER: S-EPMC6553932 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Liu FuJun F Liu XueXia X Liu Xin X Li Ting T Zhu Peng P Liu ZhengYang Z Xue Hui H Wang WenJuan W Yang XiuLan X Liu Juan J Han WenLing W

Molecular & cellular proteomics : MCP 20190313 6

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene family that has been implicated in male reproduction. CMTM4 is an evolutionarily conserved member that is highly expressed in the testis. However, its function in male fertility remains unknown. Here, we demonstrate that CMTM4 is associated with spermatogenesis and sperm quality. Using Western blotting and immunohistochemical analyses, we found CMTM4 expression to be decreased in poor-quality hum ...[more]

PMID: 30867229

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Project description:BackgroundPhosphorus (P) is one of the most essential macronutrients for crops. The growth and yield of peanut (Arachis hypogaea L.) are always limited by P deficiency. However, the transcriptional and metabolic regulatory mechanisms were less studied. In this study, valuable phenotype, transcriptome and metabolome data were analyzed to illustrate the regulatory mechanisms of peanut under P deficiency stress.ResultIn present study, two treatments of P level in deficiency with no P application (-P) and in sufficiency with 0.6 mM P application (+ P) were used to investigate the response of peanut on morphology, physiology, transcriptome, microRNAs (miRNAs), and metabolome characterizations. The growth and development of plants were significantly inhibited under -P treatment. A total of 6088 differentially expressed genes (DEGs) were identified including several transcription factor family genes, phosphate transporter genes, hormone metabolism related genes and antioxidant enzyme related genes that highly related to P deficiency stress. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that 117 genes were annotated in the phenylpropanoid biosynthesis pathway under P deficiency stress. A total of 6 miRNAs have been identified significantly differential expression between + P and -P group by high-throughput sequencing of miRNAs, including two up-regulated miRNAs (ahy-miR160-5p and ahy-miR3518) and four down-regulated miRNAs (ahy-miR408-5p, ahy-miR408-3p, ahy-miR398, and ahy-miR3515). Further, the predicted 22 target genes for 6 miRNAs and cis-elements in 2000 bp promoter region of miRNA genes were analyzed. A total of 439 differentially accumulated metabolites (DAMs) showed obviously differences in two experimental conditions.ConclusionsAccording to the result of transcripome and metabolome analyses, we can draw a conclusion that by increasing the content of lignin, amino acids, and levan combining with decreasing the content of LPC, cell reduced permeability, maintained stability, raised the antioxidant capacity, and increased the P uptake in struggling for survival under P deficiency stress.

Dataset Information

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

Publications

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

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