ArticlePloS one2015
Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Biomechanics and mechanical signaling in the ovary: a systematic review.Journal of assisted reproduction and genetics · 2018Pooled it
- Rapamycin preserves primordial follicles during closed‑system vitrification of mouse ovarian tissue.Clinical and experimental reproductive medicine · 2026Article
- Therapeutic Effects of Stromal Stem Cells Derived from Ovarian Tissue in a Cyclophosphamide-Induced Rat Model of Ovarian Failure.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- BEZ235-Mediated PI3K/mTOR dual inhibition improves ovarian follicle survival in a preclinical model.Reproductive biology and endocrinology : RB&E · 2025Article
- Follicular metabolic dysfunction, oocyte aneuploidy and ovarian aging: a review.Journal of ovarian research · 2025Review
- Perspectives on biomarkers of reproductive aging for fertility and beyond.Nature aging · 2024Review
- Potential Therapeutic Options for Premature Ovarian Insufficiency: Experimental and Clinical Evidence.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Making a good egg: human oocyte health, aging, and in vitro development.Physiological reviews · 2023Review
- The mTOR Inhibitor Rapamycin Counteracts Follicle Activation Induced by Ovarian Cryopreservation in Murine Transplantation Models.Medicina (Kaunas, Lithuania) · 2023Article
- Rumen-protected glucose stimulates the secretion of reproductive hormones and the mTOR/AKT signaling pathway in the ovaries of early postpartum.Scientific reports · 2023Article
- The Aging Ovary and the Tales Learned Since Fetal Development.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2023Review
- Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants.Frontiers in endocrinology · 2023Review
- Current progress onFrontiers in cell and developmental biology · 2023Review
- DNA Damage Stress Response and Follicle Activation: Signaling Routes of Mammalian Ovarian Reserve.International journal of molecular sciences · 2022Review
- Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.Reproductive biology and endocrinology : RB&E · 2022Article
- Therapeutic options for premature ovarian insufficiency: an updated review.Reproductive biology and endocrinology : RB&E · 2022Review
- Article
- Nuclear Receptors in Ovarian Function.Advances in experimental medicine and biology · 2022Article
- The Interconnections Between Somatic and Ovarian Aging in Murine Models.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Review
- Integrated stress response control of granulosa cell translation and proliferation during normal ovarian follicle development.Molecular human reproduction · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator) before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.