ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 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
- Potential Effects of Prepubertal Exposure to Perfluorooctane Sulfonic Acid on the First Wave of Folliculogenesis in Young CD-1 Mice.Birth defects research · 2026Article
- Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.Reproduction & fertility · 2026Review
- DNA damage response signaling in oocytes from an oncofertility perspective†.Biology of reproduction · 2026Review
- Flaxseed Lignans Alleviates Doxorubicin-Induced Premature Ovarian Insufficiency in Adult Female Mice.Reproductive sciences (Thousand Oaks, Calif.) · 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
- Exposure to Long- and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: AnEnvironmental health perspectives · 2025Article
- An overview of different methods to establish a murine premature ovarian failure model.Animal models and experimental medicine · 2024Review
- Oocyte death is triggered by the stabilization of TAp63α dimers in response to cisplatin.Cell death & disease · 2024Article
- Effect of Serotonin (5-Hydroxytryptamine) on Follicular Development in Porcine.International journal of molecular sciences · 2024Article
- Rejuvenation of aged oocyte through exposure to young follicular microenvironment.Nature aging · 2024Article
- Three-Dimensionally Printed Agarose Micromold Supports Scaffold-Free Mouse Ex Vivo Follicle Growth, Ovulation, and Luteinization.Bioengineering (Basel, Switzerland) · 2024Article
- 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
- Maximizing ovarian function and fertility following chemotherapy in premenopausal patients: Is there a role for ovarian suppression?Gynecologic oncology reports · 2024Review
- Anti-Proliferative and Apoptotic Activities ofLife (Basel, Switzerland) · 2023Article
- Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis.Molecular pharmaceutics · 2023Article
- A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.Lab on a chip · 2023Article
- Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis.Cell death & disease · 2023Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Doxorubicin (DOX), one of the most commonly used anticancer medications, has been reported to affect fertility by damaging ovarian follicles; however, the dose-dependent toxicity of DOX on the dynamic follicle development and oocyte maturation has not been well-defined. Our objective is to determine the effects of human-relevant exposure levels of DOX on follicular functions across developmental time. In vitro cultured multilayered secondary mouse follicles were treated with DOX at 0, 2, 20, 100, and 200 nM for 24 h, and follicle development, hormone secretion, and oocyte maturation were analyzed. DOX caused dose-dependent toxicity on follicle growth, survival, and secretion of 17β-estradiol (E2). At 200 nM, DOX induced DNA damage and apoptosis in follicle somatic cells first and then in oocytes, which was correlated with the uptake of DOX first to the somatic cells followed by germ cells. Follicles treated with DOX at 0, 2, and 20 nM showed similar oocyte metaphase II (MII) percentages after in vitro oocyte maturation; however, 20 nM DOX significantly increased the number of MII oocytes with abnormal spindle morphology and chromosome misalignment. In an effort to harmonize the in vitro study to in vivo treatment, dose-dependent toxicity on oocyte meiotic maturation was found in 16-day-old CD-1 mice treated with DOX at 0, 0.4, 2, and 10 mg/kg, consistent with the in vitro oocyte maturation outcomes. Our study demonstrates that DOX has dose-dependent toxicity on ovarian follicle development, hormone secretion, and oocyte maturation, which are three key factors to support the female reproductive and endocrine functions.
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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.