ArticleScientific reports2018
Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Quantitative proteomic analysis of pathological and physiological ovarian aging: model evaluation, molecular mechanisms, and identification of early biomarkers and therapeutic targets.Journal of ovarian research · 2025Article
- Absence of CDK12 in oocyte leads to female infertility.Cell death & disease · 2025Article
- Role of epigenetic regulation in diminished ovarian reserve.Journal of assisted reproduction and genetics · 2025Review
- Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Searching for the 'X' factor: investigating the genetics of primary ovarian insufficiency.Journal of ovarian research · 2024Review
- Loss of FMRP affects ovarian development and behaviour through multiple pathways in a zebrafish model of fragile X syndrome.Human molecular genetics · 2024Article
- Making a good egg: human oocyte health, aging, and in vitro development.Physiological reviews · 2023Review
- Article
- Current understanding of the genomic abnormities in premature ovarian failure: chance for early diagnosis and management.Frontiers in medicine · 2023Review
- The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis.Journal of clinical medicine · 2022Article
- The Clinical Application of Growth Hormone and Its Biological and Molecular Mechanisms in Assisted Reproduction.International journal of molecular sciences · 2022Review
- Mitochondria: emerging therapeutic strategies for oocyte rescue.Reproductive sciences (Thousand Oaks, Calif.) · 2022Review
- Article
- Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Review
- Mechanisms of ovarian aging.Reproduction (Cambridge, England) · 2021Review
- The significance of FMR1 CGG repeats in Chinese women with premature ovarian insufficiency and diminished ovarian reserve.Reproductive biology and endocrinology : RB&E · 2020Article
- Article
- Not many shoulders of giants to stand on these days.Journal of assisted reproduction and genetics · 2018Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target.
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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.