{"title":"GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.","authors":"Deshan Yin, Fei Li, Li Xia, Tianjiao Wei, Chunhua Shan, Zhe Zhang, Rui Wei","doi":"10.1007/s12020-025-04245-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-025-04245-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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