Cyclophosphamide-induced animal models of ovarian dysfunction: from molecular mechanisms and modeling strategies to validation criteria
- 1School of Nursing, Henan University Of Chinese Medicine
- 2First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and National Clinical Research Center for Chinese Medicine
- 3College of Traditional Chinese Medicine, Henan University of Chinese Medicine
Abstract
The prevalence of ovarian dysfunction is rising annually and trending toward younger populations, significantly compromising the quality of life and reproductive potential of women in their prime childbearing years. Given the multifactorial etiology and complex pathogenesis, ovarian dysfunction requires robust animal models to elucidate underlying mechanisms and evaluate therapeutic efficacy. Due to its well-documented gonadotoxicity, cyclophosphamide (CTX) has become a cornerstone in establishing standardized models of ovarian dysfunction. This review provides a systematic summary of the core mechanisms underlying CTX-induced ovarian dysfunction, with an emphasis on their interconnected regulatory network encompassing oxidative stress, DNA damage and defective repair, apoptosis, cellular senescence, immune-inflammatory responses, autophagy, and ferroptosis. Furthermore, it delineates modeling protocols, encompassing animal species selection, dosing regimens, validation criteria, and outcome evaluation. Several critical limitations in current modeling practices have been identified, including significant inter-study variability in dosing regimens, the indiscriminate application of uniform doses across distinct disease stages, and a dearth of standardized benchmarks for both model establishment and outcome evaluation. Future studies should clarify the mechanistic crosstalk in CTX-induced ovarian injury and identify potential therapeutic targets. Moreover, it is essential to delineate the dose-response relationships, establishment criteria, and evaluation metrics specifically tailored to DOR, POI, and POF. Establishing standardized, graded modeling protocols is critical to providing a reliable framework for the clinical translation of basic research findings.
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BibTeX
@article{wang2026cyclophosphamideinduced,
title = {{Cyclophosphamide-induced animal models of ovarian dysfunction: from molecular mechanisms and modeling strategies to validation criteria}},
author = {Yanxi Wang and Jixing Cao and Zheng Gong and Saihua Ma and Yuge Yan and Tian Yang and Rongfan Wu and Puyu Hu and Liping Yang and Xiaoyan Zou and Tian Xia},
journal = {Journal of Ovarian Research},
year = {2026},
month = jul,
doi = {10.1186/s13048-026-02198-4},
url = {https://doi.org/10.1186/s13048-026-02198-4},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cyclophosphamide-induced animal models of ovarian dysfunction: from molecular mechanisms and modeling strategies to validation criteria
AU - Yanxi Wang
AU - Jixing Cao
AU - Zheng Gong
AU - Saihua Ma
AU - Yuge Yan
AU - Tian Yang
AU - Rongfan Wu
AU - Puyu Hu
AU - Liping Yang
AU - Xiaoyan Zou
AU - Tian Xia
PY - 2026
DA - 2026/07/01
JO - Journal of Ovarian Research
DO - 10.1186/s13048-026-02198-4
UR - https://doi.org/10.1186/s13048-026-02198-4
AB - The prevalence of ovarian dysfunction is rising annually and trending toward younger populations, significantly compromising the quality of life and reproductive potential of women in their prime childbearing years. Given the multifactorial etiology and complex pathogenesis, ovarian dysfunction requires robust animal models to elucidate underlying mechanisms and evaluate therapeutic efficacy. Due to its well-documented gonadotoxicity, cyclophosphamide (CTX) has become a cornerstone in establishing standardized models of ovarian dysfunction. This review provides a systematic summary of the core mechanisms underlying CTX-induced ovarian dysfunction, with an emphasis on their interconnected regulatory network encompassing oxidative stress, DNA damage and defective repair, apoptosis, cellular senescence, immune-inflammatory responses, autophagy, and ferroptosis. Furthermore, it delineates modeling protocols, encompassing animal species selection, dosing regimens, validation criteria, and outcome evaluation. Several critical limitations in current modeling practices have been identified, including significant inter-study variability in dosing regimens, the indiscriminate application of uniform doses across distinct disease stages, and a dearth of standardized benchmarks for both model establishment and outcome evaluation. Future studies should clarify the mechanistic crosstalk in CTX-induced ovarian injury and identify potential therapeutic targets. Moreover, it is essential to delineate the dose-response relationships, establishment criteria, and evaluation metrics specifically tailored to DOR, POI, and POF. Establishing standardized, graded modeling protocols is critical to providing a reliable framework for the clinical translation of basic research findings.
SN - 1757-2215
ER -