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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.


Dong-Mei Gan, Ping-Ping Zhang, Jian-Ping Zhang, Shu-Xia Ding, Jie Fang, Yang Liu. KISS1/KISS1R mediates Sertoli cell apoptosis via the PI3K/AKT signalling pathway in a high‑glucose environment. Molecular medicine reports. 2021 Jun;23(6)

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PMID: 33899117

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