ArticleMolecular human reproduction2020
Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging.
Article in Molecular human reproduction, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- Fertility in breast cancer survivorship: a scoping review.Journal of cancer survivorship : research and practice · 2026Review
- Innovative Xenotransplantation of Reconstructed Human Artificial Ovary Using 3D-Printed Scaffolds and Umbilical Cord Mesenchymal Stem Cells.International journal of fertility & sterility · 2026Article
- The role of anti-Müllerian hormone as a therapeutic agent to preserve the ovarian follicle pool during chemotherapy.Journal of assisted reproduction and genetics · 2026Review
- Article
- hAECs restore follicular development in premature ovarian insufficiency via IGFBP2/IGF1R-mediated intercellular communication.Stem cell research & therapy · 2026Article
- Female fertility preservation: 25 years of progress, expanding indications and future prospects.Human reproduction update · 2026Review
- Hydrogen-generating nanomodulators for metabolic repair and functional recovery in ovarian tissue transplantation.Journal of nanobiotechnology · 2026Article
- Multi-target modulation of the homologous recombination pathway by resveratrol promotes DNA damage repair in POI: integrated network pharmacology, molecular dynamics simulation, and experimental validation.International journal of surgery (London, England) · 2026Article
- Mesenchymal stem cell therapy for premature ovarian insufficiency: progress and challenges.Journal of ovarian research · 2026Review
- From Genes to Lives: Integrating the Complexities of Primary Ovarian Insufficiency.International journal of molecular sciences · 2026Review
- Molecular Actions of Cyclophosphamide (CPA) in the Ovaries of Rats with Mammary Neoplasia.Cancer management and research · 2026Article
- Fertility preservation and reproductive outcomes in young women with breast and gynecological cancers: a new challenge for the clinician.Frontiers in oncology · 2026Review
- IVF outcomes in cancer survivors: lower ovarian response and early embryo development but comparable success in frozen embryo transfer cycles - a retrospective cohort study.Frontiers in endocrinology · 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
- Fertility Protection in Female Cancer Patients: From Molecular Mechanisms of Gonadotoxic Therapies to Pharmacotherapeutic Possibilities.International journal of molecular sciences · 2025Review
- Urolithin A Protects Ovarian Reserve Via Inhibiting PI3K/Akt Signaling and Preventing Chemotherapy-Induced Follicle Apoptosis.Biology · 2025Article
- Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?Human reproduction (Oxford, England) · 2025Article
- Metformin protects prepubertal mice ovarian reserve against cyclophosphamide via regulation of the PI3K/Akt/mTOR signaling pathway and Yap-1.Journal of ovarian research · 2024Article
- MSCs-derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K/AKT/mTOR axis.Journal of ovarian research · 2024Article
- Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system.Reproductive biology and endocrinology : RB&E · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Among the investigated mechanisms of chemotherapy-induced damage to human primordial follicle reserve are induction of DNA double-strand breaks (DSBs) and resultant apoptotic death, stromal-microvascular damage and follicle activation. Accumulating basic and translational evidence suggests that acute exposure to gonadotoxic chemotherapeutics, such as cyclophosphamide or doxorubicin, induces DNA DSBs and triggers apoptotic death of primordial follicle oocytes within 12-24 h, resulting in the massive loss of ovarian reserve. Evidence also indicates that chemotherapeutic agents can cause microvascular and stromal damage, induce hypoxia and indirectly affect ovarian reserve. While it is possible that the acute reduction of the primordial follicle reserve by massive apoptotic losses may result in delayed activation of some primordial follicles, this is unlikely to be a predominant mechanism of loss in humans. Here, we review these mechanisms of chemotherapy-induced ovarian reserve depletion and the potential reasons for the discrepancies among the studies. Based on the current literature, we propose an integrated hypothesis that explains both the acute and delayed chemotherapy-induced loss of primordial follicle reserve in the human ovary.
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