Yin Deshan, Li Fei, Xia Li, Wei Tianjiao, Shan Chunhua, Zhang Zhe, Wei Rui
Department of Endocrinology and Metabolism, State Key Laboratory of Female Fertility Promotion, Peking University Third Hospital, Beijing, China.
Department of Urology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
Endocrine. 2025 May 10. doi: 10.1007/s12020-025-04245-4.
Glucagon-like peptide-1 receptor (GLP-1R) agonists exert multiple beneficial effects. However, their effects on reproduction system are controversial. Here, we aimed to investigate their effects on male reproduction and provide safety evidence for future clinical use.
Male diabetic mice and aged mice were treated with liraglutide or vehicle, and sperm concentration and motility were assessed. The expression and location of GLP-1R in testicular tissues and in four testicular cell lines (spermatogonia, spermatocytes, Leydig cells, and Sertoli cells) were detected. Cauda epididymis and testicular cells were treated with liraglutide, semaglutide or vehicle, and sperm motility and cell proliferation were detected to determine the direct effect of GLP-1R agonists. Global Glp1r knockout mice were constructed, and testicular morphology, sperm concentration and motility were detected to confirm the effects of GLP-1R signaling on male reproduction.
Liraglutide significantly reduced blood glucose levels, but did not improve sperm parameters in diabetic mice. No significant differences were observed between liraglutide and control group in aged mice. GLP-1R was expressed in testicular tissues and all four cell lines, with the highest expression in Leydig cells. Liraglutide or semaglutide had no impacts on sperm count and motility in vitro, and had no effects on cell proliferation in four cell lines. The Glp1r knockout mice exhibited higher blood glucose levels and preserved normal testicular morphology, but their sperm concentration was higher than that in wildtype mice.
GLP-1R agonists have no detrimental effect on sperm concentration and motility in vivo and in vitro, while GLP-1R absence increase the sperm concentration.
胰高血糖素样肽-1受体（GLP-1R）激动剂具有多种有益作用。然而，它们对生殖系统的影响存在争议。在此，我们旨在研究其对雄性生殖的影响，并为未来临床应用提供安全性证据。
对雄性糖尿病小鼠和老年小鼠用利拉鲁肽或赋形剂进行处理，并评估精子浓度和活力。检测GLP-1R在睾丸组织和四种睾丸细胞系（精原细胞、精母细胞、睾丸间质细胞和支持细胞）中的表达和定位。用利拉鲁肽、司美格鲁肽或赋形剂处理附睾尾和睾丸细胞，检测精子活力和细胞增殖，以确定GLP-1R激动剂的直接作用。构建全身性Glp1r基因敲除小鼠，检测睾丸形态、精子浓度和活力，以证实GLP-1R信号通路对雄性生殖的影响。
利拉鲁肽显著降低血糖水平，但未改善糖尿病小鼠的精子参数。在老年小鼠中，利拉鲁肽组与对照组之间未观察到显著差异。GLP-1R在睾丸组织和所有四种细胞系中均有表达，在睾丸间质细胞中表达最高。利拉鲁肽或司美格鲁肽对体外精子数量和活力无影响，对四种细胞系的细胞增殖也无作用。Glp1r基因敲除小鼠血糖水平较高，睾丸形态正常，但其精子浓度高于野生型小鼠。
GLP-1R激动剂在体内和体外对精子浓度和活力均无有害影响，而缺乏GLP-1R会增加精子浓度。
