Selenium Nanoparticles Modulate Steroidogenesis-Related Genes and Improve Ovarian Functions via Regulating Androgen Receptors Expression in Polycystic Ovary Syndrome Rat Model

Abstract

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.

Comparable Toxicity of Surface-Modified TiO2 Nanoparticles: An In Vivo Experimental Study on Reproductive Toxicity in Rats

“…Moreover, our findings indicate that the ovarian endocrine components of TiO 2 -and TiO 2 /SA-treated animals are targets of NPs, as evidenced by the increase in abnormal (apoptosis and necrosis-like) morphologies of secretory cells, large atretic follicles, severe inflammatory cell infiltration, lymphocytosis, and vascular dilation and congestion (Figure 2C-F). The observed ovarian injuries with irregular cycles and significantly higher fractional contributions of ovaries in the TiO 2 and TiO 2 /SA groups could be associated with the structural damage of the mitochondria and nuclei of ovarian cells, including mitochondrial swelling, rupture, chromatin condensation, and irregularity in the nuclear membrane, as previously reported by Wang et al [48], but also with modifications in the expression of genes related to estrogen and progesterone synthesis and metabolism [49,50]. It was found that the application of TiO 2 NPs upregulated Cyp17a1, which is responsible for enhanced estradiol production [51], which is important considering that the expression levels of estradiol and progesterone, secreted by granulosa and luteal cells, are typically used to estimate ovarian endocrine function [52].…”

Androgen excess: a hallmark of polycystic ovary syndrome

“…One study demonstrated that SeNPs reduce androgen production by downregulating the expression of key steroidogenic enzymes, including STAR, CYP11A1, CYP17A1, and HSD17B3, while increasing the expression of CYP19α1. Additionally, the block of AR expression was found ( 131 ). Fourteen days of low-dose SeNP supplementation normalizes the aberrant metabolic features of PCOS and inhibits the expression of inflammatory factors, including IL-6, TNF-α, and IL-1, via repairing the antioxidant KEAP1/NRF2 cascades ( 132 ).…”