Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis
Mkrn2 缺乏在睾丸通过 p53/PERP-mediated apoptosis 导致 teratozoospermia 和男不孕作者机构:Department of PathologyNanjing Medical UniversityNanjing 210029China Department of NeurosurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China The Academy of Medical SciencesZhengzhou UniversityZhengzhou 450001China Department of PathologyThe University of IowaIowa CityIA 52242USA
出 版 物:《Asian Journal of Andrology》 (亚洲男性学杂志(英文版))
年 卷 期:2020年第22卷第4期
页 面:414-421页
核心收录:
学科分类:1002[医学-临床医学] 100210[医学-外科学(含:普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
基 金:the National Natural Science Foundation of China(No.81270736) the China Postdoctoral Science Foundation(No.2016M600432) the Jiangsu Provincial Natural Science Foundation(No.BK20150996)
主 题:apoptosis makorin-2 p53 p53 apoptosis effector related to PMP22 spermatogenesis
摘 要:The apoptosis that occurs in the immature testis under physiological conditions is necessary for male germ cell development,whereas improper activation of apoptosis can impair spermatogenesis and cause defects in *** previously demonstrated that in mice,the makorin-2(Mkrn 2)gene is expressed exclusively in the testis and its deletion leads to male *** understand the potential molecular mechanism,in this study,we found that levels of apoptosis in the testis were abnormally high in the absence of Mkrn *** identify specific gene(s)involved,we performed digital gene expression profiling(DGE)and pathway analysis via gene set enrichment analysis(GSEA)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,and we found that MKRN2 inhibits p53 apoptosis effector related to PMP22(PERP)expression and that levels of the protein in sperm samples have an inverse correlation with infertility *** additionally indicated that PERP is a negative regulator of spermatogenesis and that its ectopic expression induces male ***,Gene Expression Omnibus(GEO)dataset analysis showed that p53,upstream of PERP,was upregulated in oligoasthenoteratozoospermia(OAT).These observations suggest that Mkrn 2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn 2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility.