Effects and Mechanism of AP39 on Ovarian Functions in Rats Exposed to Cisplatin and Chronic Immobilization Stress

Overview

Journal J Menopausal Med

Date 2024 Sep 24

PMID 39315502

Authors

Ebru Onalan

Bilgi Erbay

Ilay Kavuran Buran

Deniz Erol

Ahmet Tektemur

Tuncay Kuloglu

Ibrahim Hanifi Ozercan

Affiliations

Soon will be listed here.

Abstract

Objectives: Premature ovarian failure (POF) rat models are essential for elucidating the hormonal and ovarian molecular mechanisms of human POF diseases and developing new therapeutic agents. This study aimed to compare the applicability of chronic immobilization stress (CIS) as a POF model with that of cisplatin and to examine the impact of AP39, a mitochondrial protective agent, on ovarian function in rats treated with cisplatin and CIS.

Methods: Sixty Sprague-Dawley female rats were divided equally into six groups (10 per group): Control, Cisplatin, AP39, Cisplatin + AP39, CIS, and CIS + AP39. Ovarian dysfunction was induced with cisplatin (3 mg/kg) or CIS. Forced swim test, hormone concentrations, estrous cyclicity, histopathology, follicle counts, and molecular alterations in the ovary and mitochondria were analyzed.

Results: In the CIS and cisplatin groups, mitochondrial biogenesis, egg quality, hormonal profile, estrous cycle, and folliculogenesis significantly declined. Nonetheless, most of the parameters with undesirable results did not normalize after AP39 administration.

Conclusions: The cisplatin- and CIS-treated rats exhibited unshared deteriorated hormonal pathways and similarly disrupted gene expression patterns. Our current CIS model did not meet the human POF criteria, which include decreased estradiol levels, despite having advantages in terms of ease of modeling and reproducibility and demonstrating pathological changes similar to those observed in human POF. Therefore, rather than using this model as an POF model, using it as a representation of stress-induced ovarian dysfunction would be more appropriate.

Citing Articles

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PMID: 39704226 PMC: 11670866. DOI: 10.3892/ijmm.2024.5475.

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