ArticleEndocrinology2015
Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Does air pollution play a role in infertility?: a systematic review.Environmental health : a global access science source · 2017Pooled it
- Modulating the Gut-Ovarian Axis: Mechanistic Rationale and the Limits of Current Evidence for Probiotics in Female Reproductive Aging.Food science & nutrition · 2026Review
- Kaempferol supplementation at 150 mg/kg improves reproductive performance of aged laying hens via modulation of the gut-liver-ovary axis.Poultry science · 2026Article
- A HO-1 gene knockout using a NanoCRISPR scaffold suppresses metastasis in mouse models.Nature biomedical engineering · 2026Article
- Exploring the nexus between particulate matter and infertility: Multiple mechanistic insights and potential control strategies.iScience · 2026Review
- Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis.Diabetologia · 2026Article
- Oxidative Stress, Parity History, and Remnant Follicles in the Aged Ovary: Insights on Ovarian Cancer Risk and Protection.Antioxidants (Basel, Switzerland) · 2025Review
- Effects of heat stress on gene expression associated with antioxidant capacity of bovine early antral follicles.The Journal of veterinary medical science · 2025Article
- Article
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- Decreased glutathione synthesis in granulosa cells, but not oocytes, of growing follicles decreases fertility in mice†.Biology of reproduction · 2024Article
- Air pollution exposure in vitrified oocyte donors and male recipient partners in relation to fertilization and embryo quality.Environment international · 2024Article
- The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia.Molecular neurobiology · 2024Review
- Sedanolide Activates KEAP1-NRF2 Pathway and Ameliorates Hydrogen Peroxide-Induced Apoptotic Cell Death.International journal of molecular sciences · 2023Article
- Evaluation of Antioxidant Defence Systems and Inflammatory Status in Basketball Elite Athletes.Genes · 2023Article
- Synthetic Phenolic Antioxidants and Their Metabolites in Follicular Fluid and Association with Diminished Ovarian Reserve: A Case-Control Study.Environmental health perspectives · 2023Article
- NRF2 and the Moirai: Life and Death Decisions on Cell Fates.Antioxidants & redox signaling · 2023Review
- Se-EnrichedAntioxidants (Basel, Switzerland) · 2023Article
- Gestational Benzo[a]pyrene Exposure Destroys F1 Ovarian Germ Cells Through Mitochondrial Apoptosis Pathway and Diminishes Surviving Oocyte Quality.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Glutathione deficiency decreases lipid droplet stores and increases reactive oxygen species in mouse oocytes†.Biology of reproduction · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm(-/-) mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm(-/-) vs Gclm(+/+) ovaries. Prepubertal Gclm(-/-) and Gclm(+/+) mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm(-/-) mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm(-/-) ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm(-/-) vs Gclm(+/+) ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm(-/-) mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development.
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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.