Hsa-miR-100-3p Controls the Proliferation, DNA Synthesis, and Apoptosis of Human Sertoli Cells by Binding to SGK3

Abstract

Human Sertoli cell is required for completing normal spermatogenesis, and significantly, it has important applications in reproduction and regenerative medicine because of its great plasticity. Nevertheless, the molecular mechanisms underlying the fate decisions of human Sertoli cells remain to be clarified. Here, we have demonstrated the expression, function, and mechanism of Homo sapiens-microRNA (hsa-miR)-100-3p in human Sertoli cells. We revealed that miR-100-3p was expressed at a higher level in human Sertoli cells by 10% fetal bovine serum (FBS) than 0.5% FBS. MiR-100-3p mimics enhanced the DNA synthesis and the proliferation of human Sertoli cells, as indicated by 5-ethynyl-2′-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays. Flow cytometry showed that miR-100-3p mimics reduced the apoptosis of human Sertoli cells, and notably, we predicted and further identified serum/glucocorticoid regulated kinase family member 3 (SGK3) as a direct target of MiR-100-3p. SGK3 silencing increased the proliferation and decreased the apoptosis of human Sertoli cells, while SGK3 siRNA 3 assumed a similar role to miR-100-3p mimics in human Sertoli cells. Collectively, our study indicates that miR-100-3p regulates the fate decisions of human Sertoli cells by binding to SGK3. This study is of great significance, since it provides the novel epigenetic regulator for the proliferation and apoptosis of human Sertoli cells and it may offer a new clue for gene therapy of male infertility.

Diabetes-induced male infertility: potential mechanisms and treatment options

“…Gene therapy strategies related to male infertility patients have been conceived. Hsa-miR-100-3p provides a new epigenetic regulator for proliferation, DNA synthesis and apoptosis of human Sertoli cells by binding to SGK3, providing new clues for gene therapy of male infertility (Liu et al 2021 ). For the gene therapy for male infertility caused by problems related to testicular and sperm gene expression, related studies have reported that through testicle-mediated gene transfer (TMGT) and sperm-mediated gene transfer (SMGT) to transfer genes from somatic cells into testicle and sperm, with sperm deliberately used as a gene transfer vector (Coward et al 2007 ).…”