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

Abstract

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.

Transcriptome analysis revealed differences in the microenvironment of spermatogonial stem cells in seminiferous tubules between pre‐pubertal and adult buffaloes

“…Another important signalling pathway was the MAPK signalling pathway. This is a conserved signalling pathway that is related to the proliferation and self‐renewal of SSCs (Simon et al., 2007, Singh and Hou, 2008, Morimoto et al., 2013, Di Fiore et al., 2016, Gao et al., 2018, La et al., 2018, Wang et al., 2018, Zhao et al., 2018). The growth factors secreted by Sertoli cells regulate SSCs through the MAPK signalling pathway in the niche.…”

Effects of clinical medications on male fertility and prospects for stem cell therapy

“…Small molecule medications can affect various germ cell during spermatogenesis ( Figure 1C ). The Angiotensin I-converting enzyme competitive inhibitor captopril reduces the proliferation rate of spermatogonial stem cells ( Gao et al, 2018 ). Topiramate which used to patients with epilepsy can cause a decrease in the number of spermatogonia and spermatocytes ( Otoom et al, 2004 ), resulting in the degeneration of spermatogenic cells and the formation of multinucleated giant cells ( El et al, 2019 ), interstitial edema, and interstitial cell necrosis.…”