KISS1/KISS1R mediates Sertoli cell apoptosis via the PI3K/AKT signalling pathway in a high-glucose environment

In male patients with diabetes, reduced sperm motility and fertility are observed. KiSS-1 metastasis suppressor (KISS1)/KISS1 receptor (KISS1R) serves an important role in regulating adolescent sexual maturity and reproductive system development in mammals; however, the mechanism underlying KISS1/KISS1R in reproductive dysfunction in male patients with diabetes is not completely understood. The aim of the present study was to examine the role of KISS1/KISS1R in Sertoli cells. High glucose (HG)-induced mouse Sertoli cells were used to model diabetes in vitro. KISS1/KISS1R overexpression and knockdown were established in mouse Sertoli cells. Reverse transcription-quantitative PCR and western blotting were performed to measure the expression levels of KISS1/KISS1R and apoptosis-related proteins. Cell viability and apoptosis was assessed by performing Cell Counting Kit-8, TUNEL staining and flow cytometry assays, respectively. Western blotting was performed to assess the expression levels of PI3K/AKT signalling-related proteins. KISS1/KISS1R expression levels were downregulated in HG-induced mouse Sertoli cells compared with control cells. KISS1/KISS1R overexpression significantly suppressed HG-induced apoptosis and decrease of viability in mouse Sertoli cells. Moreover, the western blotting results indicated that KISS1/KISS1R activated PI3K/AKT signalling. Treatment with PI3K/AKT pathway inhibitor significantly reversed KISS1/KISS1R-mediated protective effects. Collectively, the results of the present study suggested that KISS1/KISS1R mediated Sertoli cell apoptosis via the PI3K/AKT signalling pathway under HG conditions, which provided reliable targets for the treatment of reproductive dysfunction in male patients with diabetes.