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.

Keywords: Androgen receptors; Ovarian histopathology and immunohistochemistry; PCOS; Selenium nanoparticles; Steroidogenesis; mRNA expression.

Fig. 1

Representative transmission electron microscopy analysis of prepared selenium nanoparticles (SeNPs) showing their size and shape

Fig. 2

Initial and final body mass index of female albino rats treated with selenium nanoparticles (SeNPs) in a polycystic ovary syndrome model. HFD, high-fat diet; L, letrozole

Fig. 3

Effect of selenium nanoparticles (SeNPs) on ovarian mRNA expression of enzymes and proteins (STAR, Steroidogenic acute regulatory protein; CYP11A1, Cytochrome P450 Family 11 Subfamily A Member 1; CYP17A1, Cytochrome P450 Family 17 Subfamily A Member 1; CYP19A1, Cytochrome P450 Family 19 Subfamily A Member 1; HSD17B3, 17-beta hydroxysteroid dehydrogenase 3) involved in steroidogenesis in a polycystic ovary syndrome rat model. HFD, high-fat diet; L, letrozole. Data are presented as the mean values with their standard errors. Columns bearing different letters indicate significant changes (P < 0.05)

Fig. 4

Photomicrographs of rat ovarian tissues show effects selenium nanoparticles (SeNPs) on the ovarian tissues in a polycystic ovary syndrome rat model. Experimental groups: (a) control, (b) obese (fed high-fat diet, HFD), (c) obese PCO (HFD + letrozole, L), (d) obese PCO treated with 0.1 SeNPs, (e) obese PCO treated with 0.2 SeNPs. (a, b) Ovarian tissue from control and obese groups shows normal architecture of ovarian tissue with follicles at different stage of development. (c) Ovarian tissue from obese PCO group shows the presence of multiple subcapsular cystic follicles. (d, e) Ovarian tissue from SeNP-treated groups shows normal developing follicles with decrease number of cystic follicles. GF, graffian follicle; CL, corpus luteum; SF, secondary follicle; PF, primary follicle; AF, antral follicle; PAF, pre-antral follicle; CF, cystic follicle (H&E × 100)

Fig. 5

Microscopic images show effect of selenium nanoparticles (SeNPs) on the androgen receptor (AR) expression in the ovarian tissues in a polycystic ovary syndrome rat model. Immunohistochemical staining of AR in different experimental groups: (a) control, (b) obese (fed high-fat diet, HFD), (c) obese PCO (HFD + letrozole, L), (d) obese PCO treated with 0.1 SeNPs, (e) obese PCO treated with 0.2 SeNPs. Short arrow signifying the positive (brown) staining of the nucleus of granulosa cells indicates the expression of AR (× 400). (f) The statistical analysis of the area percent of AR expression among the studied groups. Data are presented as the mean values with their standard errors. Columns bearing different letters indicate significant changes (P < 0.05)