ArticleMolecular human reproduction2021
Integrated stress response control of granulosa cell translation and proliferation during normal ovarian follicle development.
Article in Molecular human reproduction, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 31 citations in OpenAlex.
- cGAS-STING Signaling as a Molecular Bridge Between Inflammation, Ovarian Ageing, and Reproductive Failure.International journal of molecular sciences · 2026Review
- Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.Annual review of genetics · 2025Review
- Transplantation of UC-MSCs in ovary improves ovarian function and intermediate outcomes in IVF/ICSI cycles of POI patients: a clinical cohort study.Stem cell research & therapy · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions.Non-coding RNA research · 2025Review
- Stochastic analysis of human ovarian aging and menopause timing.Biophysical journal · 2025Article
- Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R.Human reproduction (Oxford, England) · 2025Article
- Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.American journal of obstetrics and gynecology · 2024Article
- Mathematical recapitulation of the end stages of human ovarian aging.Science advances · 2024Article
- Making a good egg: human oocyte health, aging, and in vitro development.Physiological reviews · 2023Review
- Spatio-temporal remodelling of the composition and architecture of the human ovarian cortical extracellular matrix during in vitro culture.Human reproduction (Oxford, England) · 2023Article
- The hypergonadotropic hypogonadism conundrum of classic galactosemia.Human reproduction update · 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
- Early postnatal alterations in follicular stress response and survival in a mouse model of Classic Galactosemia.Journal of ovarian research · 2022Article
- The Role of PEDF in Reproductive Aging of the Ovary.International journal of molecular sciences · 2022Article
- Harnessing the Power of Purple Sweet Potato Color andInternational journal of molecular sciences · 2022Article
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12 authors at 4 institutions in 1 country.
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Abstract
Mechanisms that directly control mammalian ovarian primordial follicle (PF) growth activation and the selection of individual follicles for survival are largely unknown. Follicle cells produce factors that can act as potent inducers of cellular stress during normal function. Consistent with this, we show here that normal, untreated ovarian cells, including pre-granulosa cells of dormant PFs, express phenotype and protein markers of the activated integrated stress response (ISR), including stress-specific protein translation (phospho-Serine 51 eukaryotic initiation factor 2α; P-EIF2α), active DNA damage checkpoints, and cell-cycle arrest. We further demonstrate that mRNAs upregulated in primary (growing) follicles versus arrested PFs mostly include stress-responsive upstream open reading frames (uORFs). Treatment of a granulosa cell (GC) line with the PF growth trigger tumor necrosis factor alpha results in the upregulation of a 'stress-dependent' translation profile. This includes further elevated P-eIF2α and a shift of uORF-containing mRNAs to polysomes. Because the active ISR corresponds to slow follicle growth and PF arrest, we propose that repair and abrogation of ISR checkpoints (e.g. checkpoint recovery) drives the GC cell cycle and PF growth activation (PFGA). If cellular stress is elevated beyond a threshold(s) or, if damage occurs that cannot be repaired, cell and follicle death ensue, consistent with physiological atresia. These data suggest an intrinsic quality control mechanism for immature and growing follicles, where PFGA and subsequent follicle growth and survival depend causally upon ISR resolution, including DNA repair and thus the proof of genomic integrity.
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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.