| Title: | Estradiol ameliorates metformin-inhibited Sertoli cell proliferation via AMPK/TSC2/mTOR signaling pathway |
| Author(s): | Zhang JJ; Li YQ; Wang YS; Chen L; Wang XZ; |
| Address: | "Chongqing Key Laboratory of Forage and Herbivore, College of Veterinary Medicine, Southwest University, Chongqing, 400715, PR China. Department of Dermatology and Sexually Transmitted Disease, The Fifth People's Hospital of Chongqing, Chongqing, 400062, PR China. Chongqing Key Laboratory of Forage and Herbivore, College of Veterinary Medicine, Southwest University, Chongqing, 400715, PR China. Electronic address: xianzhong_wang@aliyun.com" |
| DOI: | 10.1016/j.theriogenology.2021.08.030 |
| ISSN/ISBN: | 1879-3231 (Electronic) 0093-691X (Linking) |
| Abstract: | "Metformin is a commonly used for treating type 2 diabetes and it acts on a variety of organs including the male reproductive system. 17beta-estradiol plays an important role in Sertoli cell (SC) proliferation which determines the germ cell development and spermatogenesis. The aim of this study is to investigate the effect of metformin on immature chicken SC proliferation and the potential mechanisms by which 17beta-estradiol regulate this process. Results showed that metformin significantly inhibited SC proliferation, whereas 17beta-estradiol weakened the inhibitory effects of metformin on SC viability, cell growth, and cell cycle progression. SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation. In addition, SCs transfected with the miR-1764 agomir led to an improvement of proliferation capacity through down-regulating AMPKalpha2 level, which further decreased TSC2 expression and induced mTOR activation. However, the anti-proliferative effect of miR-1764 antagomir can be alleviated by 17beta-estradiol treatment via the up-expression of miR-1764 in transfected SCs. Our findings suggest appropriate dose of exogenous 17beta-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents" |
| Keywords: | AMP-Activated Protein Kinases/genetics/metabolism Animals Cell Proliferation Chickens *Estradiol/pharmacology Male *Metformin/pharmacology Sertoli Cells/cytology/*drug effects *Signal Transduction TOR Serine-Threonine Kinases/genetics/metabolism Tuberous; |
| Notes: | "MedlineZhang, Jiao Jiao Li, Ya Qi Wang, Yu Sha Chen, Liang Wang, Xian Zhong eng 2021/09/05 Theriogenology. 2021 Nov; 175:7-22. doi: 10.1016/j.theriogenology.2021.08.030. Epub 2021 Aug 28" |
