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Additionally, other studies demonstrated that 5\u2032 adenosine monophosphate-activated protein kinase (AMPK) is an upstream regulatory element of mTOR and YAP. Here, we used AMPK inhibitor (Compound C) to in vitro cultured ovaries from 10-day-old mice followed by in vivo grafting into adult hosts or to in situ treated ovaries of 3-week-old mice by intrabursal injection followed by gonadotropin stimulation. We found that the phosphorylation of ovarian mTOR and downstream proteins (ribosomal protein S6 (S6) and eukaryotic translation initiation factor 4B (eIF4B)) was upregulated following Compound C administration, whereas tuberous sclerosis complex 2 (TSC2) phosphorylation was downregulated. Additionally, treatment with Compound C increased hypoxia-inducible factor 1-alpha (Hif1a), vascular endothelial growth factor A (Vegfa), VEGF receptor 2 (Vegfr2) and connective tissue growth factor (Ctgf) mRNA levels. Furthermore, treatment of 10-day-old mice with Compound C promoted the growth of preantral and antral follicles accompanied by enhanced angiogenesis. In situ intrabursal injection with Compound C, followed by controlled ovarian hyperstimulation, increased the number of ovulated oocytes in 3-week-old mice, and these oocytes could be successfully fertilized, leading to the delivery of healthy pups. Our results demonstrated that treatment with AMPK inhibitor resulted in the activation of the mTOR signaling pathway, increases in Ctgf expression in mouse ovaries, stimulation of follicle development and promotion of ovarian angiogenesis for ovary growth.<\/jats:p>","DOI":"10.1530\/rep-16-0577","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T20:20:23Z","timestamp":1488399623000},"page":"683-694","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":37,"title":["Stimulation of ovarian follicle growth after AMPK inhibition"],"prefix":"10.1093","volume":"153","author":[{"given":"Xiaowei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology \u00a0 Center of Reproductive Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Department of Obstetrics and Gynecology \u00a0 Stanford University School of Medicine, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology \u00a0 Center of Reproductive Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology \u00a0 Stanford University School of Medicine, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-hong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology \u00a0 Stanford University School of Medicine, Stanford University, Stanford, California, 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