ArticleToxicology and applied pharmacology2019
Doxorubicin obliterates mouse ovarian reserve through both primordial follicle atresia and overactivation.
Article in Toxicology and applied pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- A closed vitrification system enables a murine ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting activity of microcystins.Reproductive toxicology (Elmsford, N.Y.) · 2020Pooled it
- In vivo labeling-based proteomic analysis of early follicle oocytes and cisplatin-induced alterations in mice.Nature communications · 2026Article
- Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.Reproduction & fertility · 2026Review
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- A Two-Hit Hypothesis for Chemotherapy-Induced Primary Ovarian Insufficiency in Asian Populations: A Population-Specific Mechanistic Framework Linking Genetic Susceptibility and Cytotoxic Stress via the PI3K-AKT-FOXO3 Axis.BioMed research international · 2026Review
- Bee-Derived Antioxidants as a Protective Strategy Against Doxorubicin-Induced Ovarian Damage.Chemistry & biodiversity · 2025Article
- Co-administration of Spirulina and L-carnitine preserves ovarian reserve in a rat model of premature ovarian insufficiency via SIRT1 regulation of oxidative stress, inflammation, and apoptosis.Scientific reports · 2025Article
- Protective effect of N-acetylcysteine in doxorubicin-induced primary ovarian failure in female rats.Turkish journal of obstetrics and gynecology · 2025Article
- Protective effect of ammonium trichloride tellurate (AS101) on ovarian injury induced by chemotherapy drug doxorubicin in rats.Journal of ovarian research · 2025Article
- Exposure to Long- and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: AnEnvironmental health perspectives · 2025Article
- L-Theanine Ameliorates Doxorubicin-Induced Ovarian Toxicity by Reducing Endoplasmic Reticulum Stress.Food science & nutrition · 2025Article
- Primordial Follicle Survival and Changes in Ovarian Vasculature May Be Independently Regulated During Chemotherapy.Endocrinology · 2025Article
- Article
- Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence.Life medicine · 2025Review
- Article
- Oocyte death is triggered by the stabilization of TAp63α dimers in response to cisplatin.Cell death & disease · 2024Article
- Article
- Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats.Journal of ovarian research · 2024Article
- Review
- The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment.Cancers · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Ovarian toxicity and infertility are major side effects of cancer therapy in young female cancer patients. We and others have previously demonstrated that doxorubicin (DOX), one of the most widely used chemotherapeutic chemicals, has a dose-dependent toxicity on growing follicles. However, it is not fully understood if the primordial follicles are the direct or indirect target of DOX. Using both prepubertal and young adult female mouse models, we comprehensively investigated the effect of DOX on all developmental stages of follicles, determined the impact of DOX on primordial follicle survival, activation, and development, as well as compared the impact of age on DOX-induced ovarian toxicity. Twenty-one-day-old CD-1 female mice were intraperitoneally injected with PBS or clinically relevant dose of DOX at 10 mg/kg once. Results indicated that DOX primarily damaged granulosa cells in growing follicles and oocytes in primordial follicles and DOX-induced growing follicle apoptosis was associated with the primordial follicle overactivation. Using the 5-day-old female mice with a more uniform primordial follicle population, our data revealed that DOX also directly promoted primordial follicle death and the DNA damage-TAp63α-C-CASP3 pathway was involved in DOX-induced primordial follicle oocyte apoptosis. Compared to 21-day- and 8-week-old female mice that were treated with the same dose of DOX, the 5-day-old mice had the most severe primordial follicle loss as well as the least degree of primordial follicle overactivation. Taken together, these results demonstrate that DOX obliterates mouse ovarian reserve through both primordial follicle atresia and overactivation and the DOX-induced ovarian toxicity is age dependent.
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