Work

Molecular Actions of Cyclophosphamide (CPA) in the Ovaries of Rats with Mammary Neoplasia

Year: 2026

Type: article

Abstract: Introduction: Women diagnosed with cancer often undergo aggressive chemotherapy that can impair fertility and lead to long-term ovarian damage, significantly affecting their quality of life. Cyclophosphamide (CPA), a chemotherapeutic agent known for its gonadotoxic effects, has been shown to reduce ovarian follicle reserves, thereby contributing to the development of primary ovarian insufficiency in both humans and animal models. This study sought to identify the molecules and intracellular signaling pathways associated with CPA's effects on ovarian tissue of rats bearing mammary tumors. Methods: To address the objective of the study, transcriptomic (RNA-Seq) and proteomic (2D-DIGE/MS) methodologies were applied. The study was conducted on rats with N-methyl-N-nitrosourea (MNU)-induced mammary neoplasia, randomly assigned to control or cyclophosphamide (CPA)-treated groups. CPA was administered intraperitoneally (50 mg/kg on day 3, then 10 mg/kg weekly until day 31). Animals were euthanized on day 34, and ovaries were collected for RNA-Seq and 2D-DIGE/MS analyses. Results: Our results demonstrated that the crucial mechanism of CPA action during follicular depletion in the ovary may be linked to CPA-induced immune cell responses. Moreover, we found that CPA may trigger apoptosis or ferroptosis of follicular cells, ultimately leading to ovarian dysfunction. Conclusion: The obtained results highlight the importance of mechanisms contributing to ovarian toxicity from cancer chemotherapy, paving the way for developing targeted strategies for ovarian protection. Further functional experiments are needed to identify substances that could effectively preserve the fertility of female cancer survivors.

Source: Cancer Management and Research

DOI: 10.2147/cmar.s557751

Authors: Anna Nynca, Sylwia Swigonska, Tomasz Molcan, Brian Petroff, Renata Ciereszko

Institutions: University of Warmia and Mazury in Olsztyn, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Polish Academy of Sciences, Michigan State University

Language: English

Topic: Reproductive Biology and Fertility

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836