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Stem Cells Dev. 2018 Aug 1;27(15):1021-1032. doi: 10.1089/scd.2017.0287. Epub 2018 Jun 29.

Somatic Angiotensin I-Converting Enzyme Regulates Self-Renewal of Mouse Spermatogonial Stem Cells Through the Mitogen-Activated Protein Kinase Signaling Pathway.

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1 State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University , Nanjing, China .
2 Center of Clinical Reproductive Medicine, Affiliated Changzhou Women's and Children's Healthcare Hospital of Nanjing Medical University , Changzhou, China .
3 Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
4 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University , Nanjing, China .
5 The Key Laboratory of Development Genes and Human Diseases, Ministry of Education, Institute of Life Sciences, Southeast University , Nanjing, China .


Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in the regulation of the renin-angiotensin system. In this study, we used reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis to confirm that somatic ACE (sACE), but not testicular ACE (tACE), is expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. sACE was found to play an important role in SSC self-renewal through the regulation of MAPK-dependent cell proliferation.


MAPKs; sACE; self-renewal; spermatogonial stem cell


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