Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Biol Trace Elem Res. 2023 Dec;201(12):5721-5733. doi: 10.1007/s12011-023-03616-0. Epub 2023 Mar 16.
Polycystic ovary syndrome (PCOS) occurs during the reproductive period in women and is characterized by reproductive, endocrine, and metabolic disorders. Androgen plays a decisive role in its pathogenesis due to the interaction between hyperandrogenism and insulin resistance, which might be improved by selenium nanoparticles (SeNPs). The present study aimed to clarify the effect of SeNPs on androgen synthesis and action in the PCOS model and the resulting effect on ovarian function. Fifty-five 7-week-old female albino rats (90-105 g) were divided equally into five groups: control (C), fed a standard diet for 11 weeks; high-fat diet (HFD) group, fed HFD for 11 weeks; HFD and letrozole (L) (HFD + L), fed HFD for 11 weeks and administrated orally with L, at a daily dose of 1 mg/kg BW, for three weeks from the 7th to 9th week of the trial; HFD + L + 0.1SeNPs and HFD + L + 0.2SeNPs groups, treated the same as HFD + L group and orally gavaged SeNPs at daily doses of 0.1 and 0.2 mg/kg BW, respectively, during the last 14 day of the experiment. Daily determination of estrous cycle was performed, and at the end of the experimental period, BMI, serum glucose, insulin, HOMA-IR, lipid profile, sex hormones, TNF-α, IL6, oxidative stress biomarkers, ovarian mRNA expression of different proteins and enzymes involved in steroidogenesis, pathological examination, and immunohistochemical staining for androgen receptor (AR) were evaluated. Treatment of SeNPs restored estrous cyclicity, decreased BMI, and insulin resistance, improved dyslipidemia, reduced serum testosterone, and improved ovarian histopathology in PCOS rats. Furthermore, the anti-inflammatory and antioxidant impacts of SeNPs were remarkably noticed. Administration of SeNPs decreased androgen synthesis and expression of ovarian AR protein by decreasing the mRNA expression of STAR, Cyp11A1, Cyp17A1, and HSD17B3 and increasing the expression of Cyp19α1. Conclusively, SeNPs decreased androgen synthesis and blocked the vicious circle initiated by excessive androgen secretion via decreased AR expression. Thus, it may effectively treat PCOS cases by eliminating its reproductive, endocrine, and metabolic dysfunctions.
多囊卵巢综合征（PCOS）发生于女性的生殖期，其特征为生殖、内分泌和代谢紊乱。雄激素在其发病机制中起决定性作用，这是由于高雄激素血症和胰岛素抵抗的相互作用所致，而硒纳米粒子（SeNPs）可能改善这种情况。本研究旨在阐明 SeNPs 对 PCOS 模型中雄激素合成和作用的影响，以及对卵巢功能的影响。将 55 只 7 周龄雌性白化大鼠（90-105g）等分为五组：对照组（C），标准饮食喂养 11 周；高脂饮食组（HFD），高脂饮食喂养 11 周；HFD 和来曲唑（L）组（HFD+L），从试验第 7 周到第 9 周，每天给予 L 口服，剂量为 1mg/kgBW，共 3 周；HFD+L+0.1SeNPs 组和 HFD+L+0.2SeNPs 组，以与 HFD+L 组相同的方式处理，并在实验的最后 14 天每天分别给予 0.1 和 0.2mg/kgBW 的 SeNPs 灌胃。每天进行发情周期的测定，在实验期末，测定 BMI、血清葡萄糖、胰岛素、HOMA-IR、血脂谱、性激素、TNF-α、IL6、氧化应激生物标志物、参与甾体生成的不同蛋白和酶的卵巢 mRNA 表达、病理学检查和雄激素受体（AR）的免疫组织化学染色。SeNPs 的治疗恢复了发情周期的周期性，降低了 BMI 和胰岛素抵抗，改善了血脂异常，降低了血清睾酮，并改善了 PCOS 大鼠的卵巢组织病理学。此外，还注意到 SeNPs 的抗炎和抗氧化作用。SeNPs 的给药通过降低 STAR、Cyp11A1、Cyp17A1 和 HSD17B3 的 mRNA 表达并增加 Cyp19α1 的表达来减少雄激素的合成和卵巢 AR 蛋白的表达。总之，SeNPs 通过降低 AR 表达来减少雄激素的合成并阻断由过多雄激素分泌引发的恶性循环，从而可能通过消除其生殖、内分泌和代谢功能障碍来有效治疗 PCOS 病例。
