ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Multidrug Resistance Protein 1 Deficiency Promotes Doxorubicin-Induced Ovarian Toxicity in Female Mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 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
- Molecular mechanisms of cisplatin resistance in ovarian cancer.Genes & diseases · 2024Review
- Effects of Cyanobacterial Harmful Algal Bloom Toxin Microcystin-LR on Gonadotropin-Dependent Ovarian Follicle Maturation and Ovulation in Mice.Environmental health perspectives · 2023Article
- Recapitulating folliculogenesis and oogenesis outside the body: encapsulated in vitro follicle growth†.Biology of reproduction · 2023Article
- A synopsis of global frontiers in fertility preservation.Journal of assisted reproduction and genetics · 2022Review
- Varied effects of doxorubicin (DOX) on the corpus luteum of C57BL/6 mice during early pregnancy†.Biology of reproduction · 2021Article
- FutureTox IV Workshop Summary: Predictive Toxicology for Healthy Children.Toxicological sciences : an official journal of the Society of Toxicology · 2021Review
- A Tiered Female Ovarian Toxicity Screening Identifies Toxic Effects of Checkpoint Kinase 1 Inhibitors on Murine Growing Follicles.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Ovarian damage from chemotherapy and current approaches to its protection.Human reproduction update · 2019Review
- Doxorubicin obliterates mouse ovarian reserve through both primordial follicle atresia and overactivation.Toxicology and applied pharmacology · 2019Article
- Chemotherapeutic agent doxorubicin alters uterine gene expression in response to estrogen in ovariectomized CD-1 adult mice†.Biology of reproduction · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Multidrug resistance protein 1 (MDR1), a phase III drug transporter that exports substrates out of cells, has been discovered in both cancerous and normal tissues. The over expression of MDR1 in cancer cells contributes to multiple drug resistance, whereas the MDR1 in normal tissues protects them from chemical-induced toxicity. Currently, the role of MDR1 in the ovary has not been entirely understood. Our objective is to determine the function of MDR1 in protecting against chemotherapy-induced ovarian toxicity. Using both the in vivo transgenic mouse model and in vitro follicle culture model, we investigated the expression of MDR1 in the ovary, the effect of MDR1 deficiency on doxorubicin (DOX)-induced ovarian toxicity, and the ovarian steroid hormonal regulation of MDR1. Results showed that the MDR1 was expressed in the ovarian epithelial cells, stroma cells, theca cell layers, endothelial cells, and luteal cells. The lack of MDR1 did not affect female ovarian function and fertility; however, its deficiency significantly exacerbated the DOX-induced ovarian toxicity in both in vivo and in vitro models. The MDR1 showed significantly higher expression levels in the ovaries at estrus and metestrus stages than those at proestrus and diestrus stages. However, this dynamic expression pattern was not regulated by the ovarian steroid hormones of estrogen (E2) and progesterone (P4) but correlated to the number and status of corpus luteum. In conclusion, our study demonstrates that the lack of MDR1 promotes DOX-induced ovarian toxicity, suggesting the critical role of MDR1 in protecting female ovarian functions during chemotherapy.
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