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Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine and metabolic disorder, it affects up to 5- 20% of women of reproductive age worldwide and accounts for anovulatory infertility. Furthermore, PCOS is associated with longterm complications as type 2 diabetes, immune disorders, cardiovascular disease, and gynecological tumors, which seriously affect the physical and mental health and quality of life of young and middle-aged women. The pathophysiology of PCOS is a highly debated and complex topic. Hyperandrogenism and insulin resistance appear to be central causes to the pathophysiology of the disease. Zinc oxide nanoparticles (ZnONPs), a novel agent to deliver zinc, have great implications in many disease therapies including insulin resistance which plays an important role in PCOS. The aim of this study is to explore the role played by ZnONPs in Letrozole- induced PCOS rat model. Materials and Methods: This study was conducted on 75 female albino rats that were divided randomly into five equal groups as follows: group I (control group), group II (PCOS group), group III (PCOS group treated with ZnONPs), group IV (PCOS group treated with metformin) and group V (PCOS group treated with both ZnONPs + metformin).PCOS had been developed in rats kept on letrozole (1 mg/kg) for 36 days (group II, III, IV,V).Treated groups (III, IV,V) received i.p ZnONPs (5mg/kg), oral metformin 300 mg/kg and both ZnONPS+ metformin respectively for the last 2 weeks of the study. All groups were subjected to: measurement of fasting serum glucose level and fasting insulin level to determine insulin resistance using (HOMA-IR index). Also, markers for dyslipidemia ,sex hormones (testosterone and estradiol), oxidative stress markers as malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and CYP17A1 gene relative expression using quantitative real time PCR technique Histopathological examination of the ovaries was done. Results: this study showed that ZnONPs significantly decreased insulin resistance (HOMA-IR), dyslipidemia, hyperandrogenism, MDA and CYP17A1 gene relative expression while significantly increased estradiol, SOD and GPX Also, histopathological study confirmed the biochemical findings. Results compared to the conventional drug (metformin), combined therapy showed additive action. Conclusion: on the basis of the results of this study it could be concluded that ZnONPs alone are able to improve metabolic changes, function and structure of the ovaries and have additive effect with metformin in experimental rat model of PCOS. |