ArticleThe Journal of endocrinology2019
Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide.
Article in The Journal of endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 158 citations in OpenAlex.
- Doxorubicin and 4-Hydroperoxycyclophosphamide Alter Mitochondrial Dynamics and miR-34 Expression in Spermatogonia and Spermatocytes In Vitro.Basic & clinical pharmacology & toxicology · 2026Article
- Imeglimin halts cyclophosphamide-induced ovarian injury: a dual modulation of TLR4/NF-κB/NLRP3-driven inflammation and AMPK/SIRT1/PGC-1α pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Ovarian puncture alters genes but not follicle growth in cyclophosphamide mice model.Reproduction & fertility · 2026Article
- Article
- Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.Journal of ovarian research · 2026Article
- Therapeutic effects of mesenchymal stem cell-derived extracellular vesicles from different tissue sources on diminished ovarian reserve and the related mechanisms.Journal of nanobiotechnology · 2026Article
- DNA damage response signaling in oocytes from an oncofertility perspective†.Biology of reproduction · 2026Review
- Fertility under fire: how chemotherapy harms the ovaries and the science fighting back?Journal of ovarian research · 2026Review
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Molecular Actions of Cyclophosphamide (CPA) in the Ovaries of Rats with Mammary Neoplasia.Cancer management and research · 2026Article
- Oocyte and embryo developmental competence following small multiple cyclophosphamide dose administrations in prepubertal female mice are comparable to adolescents.Scientific reports · 2025Article
- The role of mammalian target of rapamycin inhibitors in mitigating cyclophosphamide-induced ovarian damage in a murine model.Clinical and experimental reproductive medicine · 2025Article
- Mechanism of platelet-rich plasma in improving cyclophosphamide-induced premature ovarian failure in rats.Stem cell research & therapy · 2025Article
- Salvia miltiorrhiza extract ameliorated ovarian damage induced by cyclophosphamide in mice by multidimensional mechanisms.Journal of ovarian research · 2025Article
- Effect of autologous cytokine-rich serum and platelet-rich plasma administration on oxidative status, minerals and proinflammatory cytokines in brain and serum in cyclophosphamide-induced ovarian failure.Journal of molecular histology · 2025Article
- Granulosa cell death is a significant contributor to DNA-damaging chemotherapy-induced ovarian insufficiency†.Biology of reproduction · 2025Article
- Exposure to Long- and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: AnEnvironmental health perspectives · 2025Article
- Does gonadotoxic chemotherapy deplete the ovarian reserve through activation of primordial follicles?Human reproduction (Oxford, England) · 2025Article
- Primordial Follicle Survival and Changes in Ovarian Vasculature May Be Independently Regulated During Chemotherapy.Endocrinology · 2025Article
- Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.Journal of ovarian research · 2025Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer therapy can cause off-target effects including ovarian damage, which may result in primary ovarian insufficiency in girls and premenopausal women. Loss of ovarian follicles within the ovarian reserve leads to ovarian endocrine dysfunction and impaired fertility. Cyclophosphamide (CPA), a commonly used chemotherapeutic and immunosuppressant agent, is a gonadotoxic agent that destroys ovarian cells by crosslinking DNA. To protect the ovary against CPA damage, we sought to precisely map the mechanism by which the ovarian reserve is depleted by CPA. We found that CPA specifically depletes primordial follicles without affecting primary and secondary follicles in three independent murine strains (CD-1, C57BL/6J and BALB/cJ) in vivo. We directly tested the effect of the active metabolite of CPA, 1 μM 4-hydroxyperoxycyclophophamide (4-HC), in vitro and confirmed the loss of primordial oocytes but no change in the number of primary and secondary follicles. We demonstrated that phospho-AKT (p-AKT) and cleaved PARP (cPARP) are present in primordial oocytes 3 days after CPA injection, consistent with the role of these markers as part of the apoptotic cascade. Interestingly, p-AKT positive primordial oocytes co-expressed cPARP. Treatment of animals with specific inhibitors of apoptotic pathway components, ETP46464 and CHK2, blocked 4-HC‒induced DNA damage in vitro. These data suggest that CPA targets primordial germ cells in the ovarian reserve by stimulating apoptosis pathways. Adjuvant therapies to protect primordial germ cells from the off-target effects of CPA may reduce the risk of POI.
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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.