ArticleToxicology and applied pharmacology2014
Involvement of a volatile metabolite during phosphoramide mustard-induced ovotoxicity.
Article in Toxicology and applied pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- Prenatal and postnatal atrazine-induced endocrine and ovarian chemical biotransformation protein disruption in offspring.Journal of the Endocrine Society · 2026Article
- DNA damage response signaling in oocytes from an oncofertility perspective†.Biology of reproduction · 2026Review
- An updated look into reactive oxygen species and cyclophosphamide-induced ovarian damage.Journal of ovarian research · 2025Review
- TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.Journal of ovarian research · 2024Article
- PFOA-Induced Ovotoxicity Differs Between Lean and Obese Mice With Impacts on Ovarian Reproductive and DNA Damage Sensing and Repair Proteins.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Low dosage use of cyclophosphamide improves the survival of patients with systemic lupus erythematosus.Clinical rheumatology · 2022Article
- Protective effects of a SIRT1 inhibitor on primordial follicle activation and growth induced by cyclophosphamide: insights from a bovine in vitro folliculogenesis system.Journal of assisted reproduction and genetics · 2022Article
- The Role of Mutant p63 in Female Fertility.International journal of molecular sciences · 2021Review
- Extended adverse effects of cyclophosphamide on mouse ovarian function.BMC pharmacology & toxicology · 2021Article
- Ovarian mitochondrial and oxidative stress proteins are altered by glyphosate exposure in mice.Toxicology and applied pharmacology · 2020Article
- Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide.The Journal of endocrinology · 2019Article
- Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis.Scientific reports · 2018Article
- Obesity alters phosphoramide mustard-induced ovarian DNA repair in mice.Biology of reproduction · 2017Article
- Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells.Toxicology and applied pharmacology · 2015Article
- Ovarian xenobiotic biotransformation enzymes are altered during phosphoramide mustard-induced ovotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The finite ovarian follicle reserve can be negatively impacted by exposure to chemicals including the anti-neoplastic agent, cyclophosphamide (CPA). CPA requires bioactivation to phosphoramide mustard (PM) to elicit its therapeutic effects however; in addition to being the tumor-targeting metabolite, PM is also ovotoxic. In addition, PM can break down to a cytotoxic, volatile metabolite, chloroethylaziridine (CEZ). The aim of this study was initially to characterize PM-induced ovotoxicity in growing follicles. Using PND4 Fisher 344 rats, ovaries were cultured for 4 days before being exposed once to PM (10 or 30 μM). Following eight additional days in culture, relative to control (1% DMSO), PM had no impact on primordial, small primary or large primary follicle number, but both PM concentrations induced secondary follicle depletion (P<0.05). Interestingly, a reduction in follicle number in the control-treated ovaries was observed. Thus, the involvement of a volatile, cytotoxic PM metabolite (VC) in PM-induced ovotoxicity was explored in cultured rat ovaries, with control ovaries physically separated from PM-treated ovaries during culture. Direct PM (60 μM) exposure destroyed all stage follicles after 4 days (P<0.05). VC from nearby wells depleted primordial follicles after 4 days (P<0.05), temporarily reduced secondary follicle number after 2 days, and did not impact other stage follicles at any other time point. VC was determined to spontaneously liberate from PM, which could contribute to degradation of PM during storage. Taken together, this study demonstrates that PM and VC are ovotoxicants, with different follicular targets, and that the VC may be a major player during PM-induced ovotoxicity observed in cancer survivors.
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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.