In vitro model of premature ovarian insufficiency based on cyclophosphamide-induced mitochondrial dysfunction in granulosa cells

Abstract

BACKGROUND: Currently, there is no unified approach or effective method for treating premature ovarian insufficiency. The primary strategy is hormone replacement therapy aimed at mitigating estrogen deficiency and its associated complications. However, this therapy does not restore lost ovarian function or fertility. Thus, further research into the pathogenesis of premature ovarian insufficiency is crucial for developing alternative pathogenetically based therapies. Investigating the efficacy of various drugs in preclinical trials using cellular models holds significant promise. Experimental modeling of premature ovarian insufficiency, which closely replicates the origin and development mechanism of the human disease, can be effectively used to develop promising therapeutic approaches, in particular, for testing new drugs.

AIM: The aim of this study was to develop a new method for experimental modeling of premature ovarian insufficiency using cyclophosphamide in Wistar rats, the significant advantages of which are high reproducibility, ease of implementation, and cost-effectiveness.

MATERIALS AND METHODS: A culture of Wistar rat ovarian granulosa cells after five stages of subculturing was treated with the drug cyclophosphamide, ensuring a working concentration in the growth medium of 0.1 mg/ml, followed by incubation for six hours.

RESULTS: A cellular model of premature ovarian insufficiency has been created, which is characterized by 100% modeling efficiency, high manufacturability and environmental safety for modeling the pathological condition.

CONCLUSIONS: The model created will allow for testing the medicinal effectiveness of chemicals with a view to their further use in medicine.

Keywords

premature ovarian insufficiency / experimental model / cyclophosphamide

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