ArticleAging cell2017
The acceleration of reproductive aging in Nrg1
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial.The Lancet. Oncology · 2018Trial
- Changes in ovarian hardness and elasticity affect the development and function of secondary follicles.Scientific reports · 2026Article
- Impact of GnRH antagonist protocols versus progestin-primed ovarian stimulation on reproductive outcomes in advanced reproductive age women: a propensity score-matched retrospective cohort study.Frontiers in endocrinology · 2026Article
- Review
- Neuregulin 1 Signaling Attenuates Tumor Necrosis Factor α-Induced Female Rat Luteal Cell Death.Endocrinology · 2024Article
- Effect of globin peptide on female fertility in aging granulosa cell-specific Nrg1 knockout mice.The Journal of reproduction and development · 2024Article
- The stromal microenvironment and ovarian aging: mechanisms and therapeutic opportunities.Journal of ovarian research · 2023Review
- Accumulation of senescent cells in the stroma of aged mouse ovary.The Journal of reproduction and development · 2023Article
- Facilitation of Ovarian Response by Mechanical Force-Latest Insight on Fertility Improvement in Women with Poor Ovarian Response or Primary Ovarian Insufficiency.International journal of molecular sciences · 2023Review
- Neuregulin-1 signaling regulates cytokines and chemokines expression and secretion in granulosa cell.Journal of ovarian research · 2022Article
- Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary.Science advances · 2022Article
- Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice.Reproductive medicine and biology · 2022Article
- PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice.Frontiers in endocrinology · 2022Article
- Impacts of endometrioma on ovarian aging from basic science to clinical management.Frontiers in endocrinology · 2022Review
- Origins and evolution of extreme life span in Pacific Ocean rockfishes.Science (New York, N.Y.) · 2021Article
- Recording Electrical Currents across the Plasma Membrane of Mammalian Sperm Cells.Journal of visualized experiments : JoVE · 2021Article
- Effect of Cetrorelix administration on ovarian stimulation in aged mice.Experimental animals · 2021Article
- Alpha/Beta Hydrolase Domain-Containing Protein 2 Regulates the Rhythm of Follicular Maturation and Estrous Stages of the Female Reproductive Cycle.Frontiers in cell and developmental biology · 2021Article
- Cutting the ovarian surface improves the responsiveness to exogenous hormonal treatment in aged mice.Reproductive medicine and biology · 2020Article
- Tubulointerstitial nephritis antigen-like 1 deficiency alleviates age-dependent depressed ovulation associated with ovarian collagen deposition in mice.Reproductive medicine and biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop a new strategy for improving fertility in older women prior to menopause. In the ovary of 6-month-old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor-positive endocrine cells and (ii) actin-rich fibrotic cells expressing collagen. Both the endocrine and fibrotic cells disappeared following long-term treatment with a GnRH antagonist, indicating that the high levels of serum LH induced the survival of both cell types and the abnormal endocrine profile to reduce fertility. Moreover, follicular development to the antral stages was observed with reduced LH and the disappearance of the abnormal stromal cells. Mice treated with the GnRH antagonist regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months. We conclude that endocrine and matrix alternations occur within the ovarian stroma with increasing age and that abolishing these alternations resets the cyclical release of LH. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause.
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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.