• PMID: 31489847
• Gene Name: MKRN3
• Condition: Teratozoospermia, male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis

Qian YC, Xie YX, Wang CS, Shi ZM, Jiang CF, Tang YY, Qian X, Wang L, Jiang BH.

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 reproduction. We previously demonstrated that in mice, the makorin-2 (Mkrn 2) gene is expressed exclusively in the testis and its deletion leads to male infertility. To 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 2. To 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 levels. GSEA additionally indicated that PERP is a negative regulator of spermatogenesis and that its ectopic expression induces male infertility. Further, 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. FAU - Qian, Ying-Chen AU - Qian YC AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Xie, Yun-Xia AU - Xie YX AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Chao-Shan AU - Wang CS AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Shi, Zhu-Mei AU - Shi ZM AD - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Jiang, Cheng-Fei AU - Jiang CF AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Tang, Yun-Yi AU - Tang YY AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Qian, Xu AU - Qian X AD - Department of Pathology, Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Lin AU - Wang L AD - The Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.