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Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis
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 (Mkrn2) gene is e...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406093/ https://www.ncbi.nlm.nih.gov/pubmed/31489847 http://dx.doi.org/10.4103/aja.aja_76_19 |
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author | Qian, Ying-Chen Xie, Yun-Xia Wang, Chao-Shan Shi, Zhu-Mei Jiang, Cheng-Fei Tang, Yun-Yi Qian, Xu Wang, Lin Jiang, Bing-Hua |
author_facet | Qian, Ying-Chen Xie, Yun-Xia Wang, Chao-Shan Shi, Zhu-Mei Jiang, Cheng-Fei Tang, Yun-Yi Qian, Xu Wang, Lin Jiang, Bing-Hua |
author_sort | Qian, Ying-Chen |
collection | PubMed |
description | 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 (Mkrn2) 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 Mkrn2. 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 Mkrn2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility. |
format | Online Article Text |
id | pubmed-7406093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-74060932020-08-17 Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis Qian, Ying-Chen Xie, Yun-Xia Wang, Chao-Shan Shi, Zhu-Mei Jiang, Cheng-Fei Tang, Yun-Yi Qian, Xu Wang, Lin Jiang, Bing-Hua Asian J Androl Original Article 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 (Mkrn2) 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 Mkrn2. 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 Mkrn2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility. Wolters Kluwer - Medknow 2019-09-06 /pmc/articles/PMC7406093/ /pubmed/31489847 http://dx.doi.org/10.4103/aja.aja_76_19 Text en Copyright: © The Author(s)(2019) http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Qian, Ying-Chen Xie, Yun-Xia Wang, Chao-Shan Shi, Zhu-Mei Jiang, Cheng-Fei Tang, Yun-Yi Qian, Xu Wang, Lin Jiang, Bing-Hua Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title | Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title_full | Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title_fullStr | Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title_full_unstemmed | Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title_short | Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis |
title_sort | mkrn2 deficiency induces teratozoospermia and male infertility through p53/perp-mediated apoptosis in testis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406093/ https://www.ncbi.nlm.nih.gov/pubmed/31489847 http://dx.doi.org/10.4103/aja.aja_76_19 |
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