Quercetin modulates granulosa cell mRNA androgen receptor gene expression in dehydroepiandrosterone-induced polycystic ovary in Wistar rats via metabolic and hormonal pathways

Abstract

BackgroundIt is estimated that about 5–10% of women suffer from polycystic ovarian syndrome (PCOS) which is a major cause of female reproductive dysfunction. This study examined the role of quercetin on dehydroepiandrosterone (DHEA)-induced PCO in Wistar rats.MethodsTwenty-eight pre-pubertal female Wistar rats that are 21 days old weighing 16–21 g were sorted into four groups (n = 7). Group I served as control and was given distilled water only, Group II were injected with 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously, Group III received 100 mg/kg BW of quercetin orally and Group IV received 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously and 100 mg/kg BW of quercetin orally. Rats were sacrificed after 15 days by cervical dislocation method. Blood samples and ovaries were collected for hormonal, biochemical, and histopathological analysis and expressions of mRNA androgen receptor gene were determined using RT–qPCR. All data were analysed using one-way ANOVA.ResultsA significant decrease (p < 0.05) in the antioxidant and metabolic enzyme activity in the DHEA treated group was observed when compared with control. DHEA co-administration with quercetin showed a significant decrease in malondialdehyde and cytokines when compared with DHEA treated group. Also a significant increase in progesterone, metabolic and antioxidant enzyme activity was observed. The histopathology demonstrates a reduction in cystic and atretic cells, improved expression of BCl2, E-Cadherin and a decrease in Bax.ConclusionsQuercetin alleviated DHEA-induced PCO. These effects could be attributed to its antioxidant property.

Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review

“…However, the regulation of estrogen expression by QUR is still controversial. Contrary evidence [ 17 , 19 , 20 ] suggests that QUR reduces PCOS estrogen levels. This may be because estrogen is not always expressed too high or too low in PCOS and QUR may regulate estrogen, which is worth further investigation.…”

“…In two in vivo experiments [ 17 , 19 ], QUR inhibits androgen receptor expression in the ovaries of rats with polycystic ovary syndrome induced by dehydroepiandrosterone (DHEA). Zheng S et al [ 17 ] reported that QUR may reduce AR expression by affecting the combination of AR in specific sequences of C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (NPR2) gene promoters.…”

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis

“…For example, Khorshidi et al observed that supplementation of 1,000 mg/day quercetin for 12 weeks significantly decreased testosterone, fasting blood glucose, insulin, and homeostatic model assessment of insulin resistance of PCOS patients compared with the placebo group [ 48 ]. Quercetin alleviated the PCOS by suppressing the levels of inflammatory cytokines (IL-1 β , IL-6, and tumor necrosis factor α ) [ 49 ], increasing the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase, and reduced glutathione) and improving granulosa cell apoptosis (upregulation of Bcl-2 and downregulation of Bax) [ 50 ]. In this study, we predicted that quercetin targeted PLK1, TXNIP, and MAP3K14.…”

The role of Sirtuin 1 in the pathophysiology of polycystic ovary syndrome

“…The changes in adiponectin, adiponectin and resistin in adipose tissue induced by PCOS were also reversed to a certain extent [ 85 ]. After quercetin treatment, the following changes occurred in the rats with PCOS induced by dihydrotestosterone: the activity of progesterone, metabolic enzymes and antioxidant enzymes was significantly increased, and DHEA-induced morphological changes related to polycystic ovaries were alleviated [ 87 ]. Quercetin also significantly decreased the expression of testosterone (T), estradiol (E(2)), LH, Bax, IL-1β, IL-6 and TNF-α, increased the expression of FSH and Bcl-2, and inhibited the expression of AR.…”