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.

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.

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.

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.

AIM: To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability, morphological integrity, and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypoxic model.METHODS: In the first set of experiments, the optimal CoCl2 dose was determined by exposing ARPE-19 cell cultures to different concentrations. To evaluate the effect of ALCAR on cell viability, five groups of ARPE-19 cell culture were established that included a control group, a sham group(200 μM CoCl2), and groups that received 1, 10 and 100 mM doses of ALCAR combined with 200 μM CoCl2, respectively. The cell viability was measured by MTT assay. The morphological characteristics of cells were observed by an inverted phase contrast microscope. The levels of VEGF and HIF-1α secretion by ARPE-19 cells were detected by enzyme linked immunosorbent assay(ELISA)assay.RESULTS: ARPE-19 cells were exposed to different doses of CoCl2 in order to create a hypoxia model. Nevertheless, when exposed to a concentration of 200 μM CoCl2, a notable decrease in viability to 83% was noted. ALCAR was found to increase the cell viability at 1 mM and 10 mM concentrations, while the highest concentration(100 mM)did not have an added effect. The cell viability was found to be significantly higher in the groups treated with a concentration of 1 mM and 10 mM ALCAR compared to the Sham group(P=0.041, P=0.019, respectively). The cell viability and morphology remained unaffected by the greatest dose of ALCAR(100 mM). The administration of 10 mM ALCAR demonstrated a statistically significant reduction in the levels of VEGF and HIF-1α compared with the Sham group(P=0.013, P=0.033, respectively).CONCLUSION: The findings from the current study indicate that ALCAR could represent a viable therapeutic option with the potential to open up novel treatment pathways for retinal diseases, particular relevance for age-related macular degeneration(AMD). However, to fully elucidate ALCAR's application potential in retinal diseases, additional investigation is necessary to clearly define the exact mechanisms involved.