ArticleThe Journal of biological chemistry2015
Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation causes premature ovarian failure.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Platelet-rich plasma and folliculogenesis: a systematic mechanistic review and computational pathway analysis.Frontiers in reproductive health · 2026Pooled it
- Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer.Oncogene · 2025Article
- Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via β2 Adrenergic Receptor Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.Zoological research · 2024Article
- MicroRNA-144-3p protects against chemotherapy-induced apoptosis of ovarian granulosa cells and activation of primordial follicles by targeting MAP3K9.European journal of medical research · 2023Article
- Aged and induced-premature ovarian failure mouse models affect diestrus profile and ovarian features.PloS one · 2023Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Article
- Melatonin Signaling Pathways Implicated in Metabolic Processes in Human Granulosa Cells (KGN).International journal of molecular sciences · 2022Article
- Effects of 4-vinylcyclohexene diepoxide on the cell cycle, apoptosis, and steroid hormone secretion of goat ovarian granulosa cells.In vitro cellular & developmental biology. Animal · 2022Article
- Long non-coding RNA BBOX1 antisense RNA 1 increases the apoptosis of granulosa cells in premature ovarian failure by sponging miR-146b.Bioengineered · 2022Article
- Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure.Stem cell research & therapy · 2021Review
- Shared aspects of mRNA expression associated with oocyte maturation failure in humans and rhesus monkeys indicating compromised oocyte quality.Physiological genomics · 2021Article
- Value of serum and follicular fluid sirtuin (SIRT)1 and SIRT2 protein levels in predicting the outcome of assisted reproduction.Annals of translational medicine · 2021Article
- Article
- Article
- Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway.International journal of endocrinology · 2020Article
- Hormone-Like Effects of 4-Vinylcyclohexene Diepoxide on Follicular Development.Frontiers in cell and developmental biology · 2020Article
- Role of Dietary Amino Acids and Nutrient Sensing System in Pregnancy Associated Disorders.Frontiers in pharmacology · 2020Review
- Ovarian damage from chemotherapy and current approaches to its protection.Human reproduction update · 2019Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular basis of ovarian folliculogenesis and etiopathogenesis of premature ovarian failure (POF), a common cause of infertility in women, are not fully understood. Mechanistic target of rapamycin complex 2 (mTORC2) is emerging as a central regulator of cell metabolism, proliferation, and survival. However, its role in folliculogenesis and POF has not been reported. Here, we showed that the signaling activity of mTORC2 is inhibited in a 4-vinylcyclohexene diepoxide (VCD)-induced POF mouse model. Notably, mice with oocyte-specific ablation of Rictor, a key component of mTORC2, demonstrated POF phenotypes, including massive follicular death, excessive loss of functional ovarian follicles, abnormal gonadal hormone secretion, and consequently, secondary subfertility in conditional knock-out (cKO) mice. Furthermore, reduced levels of Ser-473-phosphorylated Akt and Ser-253-phosphorylated Foxo3a and elevated pro-apoptotic proteins, Bad, Bax, and cleaved poly ADP-ribose polymerase (PARP), were observed in cKO mice, replicating the signaling alterations in 4-VCD-treated ovaries. These results indicate a critical role of the Rictor/mTORC2/Akt/Foxo3a pro-survival signaling axis in folliculogenesis. Interestingly, loss of maternal Rictor did not cause obvious developmental defects in embryos or placentas from cKO mice, suggesting that maternal Rictor is dispensable for preimplantation embryonic development. Our results collectively indicate key roles of Rictor/mTORC2 in folliculogenesis, follicle survival, and female fertility and support the utility of oocyte-specific Rictor knock-out mice as a novel model for POF.
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Registered trials
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