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

Background It 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. Methods Twenty-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. Results A 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. Conclusions Quercetin alleviated DHEA-induced PCO. These effects could be attributed to its antioxidant property.

Ovarian Metabolic activity in Dehydroepiandrosterone-Induced Polycystic Ovary in Wistar rats Treated with Aspirin.

OBJECTIVES: Polycystic ovary syndrome (PCOS) represents 75% of the cases of anovulatory infertility. The aim of this study was to investigate the role of aspirin on dehydroepiandrosterone (DHEA) - induced polycystic ovary syndrome in Wistar rats. METHODS: Twenty eight (28) pre-pubertal female Wistar rats of 21 days old weighing 16 - 21 g were divided into 4 groups (7 rats/group) and treated as follows; group I received distilled water and served as Control; Group II received 6 mg/100 g body weight DHEA in 0.2 ml of oil subcutaneously to induce PCOS. Group III received 7.5 mg/kg of aspirin orally; Group IV received 6 mg/100kg of body weight of DHEA in 0.2ml of oil subcutaneously and 7.5 mg/kg of aspirin orally. After 15 days of administration, the rats were slaughtered by cervical dislocation. Blood samples and ovaries were collected for reproductive hormonal analysis, biochemical and histopathological analysis. The expressions of mRNA androgen receptor (AR) gene in the ovary were determined by real time reverse transcriptase polymerase chain reaction (qPCR). All the data was analyzed using one way ANOVA with the Graph pad prism software version 6. A p<0.05 was considered significant. RESULTS: The results obtained showed that dehydroepiandrosterone treatment caused significant decrease (p<0.05) in total protein, superoxide Dismutase (SOD), glutathione-s- transferase (GST), Ca2+ ATPase, and significant increase (p<0.05) in malondialdehyde, vascular endothelial growth factor, tumor necrosis factor and estrogen as compared to Controls. The group co-administered with DHEA and aspirin showed significant increases in SOD, GST, CAT, GSH, Progesterone, Ca2+ ATPase, Na+ ATPase, H+ ATPase and significant reduction (p<0.05) in malondialdehyde, VEGF, TNF-α and estrogen as compared with the DHEA group. The histopathological analysis showed reductions in cystic fibrosis, atretic ovaries, increased expression of Bcl-2 and E- Cadherin and reduced Bax expression in the group that received Aspirin and DHEA. CONCLUSION: This study clearly demonstrates that Aspirin has ameliorating effects against polycystic ovary syndrome via anti-inflammatory and hormonal modulatory pathways.

Vitamin C suppresses ovarian pathophysiology in experimental polycystic ovarian syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS), also known as the Stein-Leventhal syndrome is one of the most common causes of anovulation, infertility and hyperandrogenism in women, affecting between 5-10 % of women of reproductive age (12-35 years) worldwide. Despite substantial effort to define the cause of PCOS, its pathophysiology remains poorly understood. Consequently, determining the mechanisms of PCOS and the possible treatment is the major goal of medical research in endocrine and reproductive physiology. AIM: To investigate the mechanism of ovarian metabolic changes in dehydroepiandrosterone (DHEA)-induced polycystic ovary in Wistar rats treated with vitamin C. METHODS: Twenty-eight immature female Wistar rats weighing (16-21 g) were randomly divided into four groups (n = 7/group): group I served as control and was given water, group II were injected with DHEA (6 mg/100 g in 0.2 ml corn oil subcutaneously to induce PCOS condition), group III received 150 mg/kg BW of Vitamin C orally, group IV were co-administered with 6 mg/kg BW DHEA in 0.2 ml of corn oil subcutaneously and 150 mg/kg BW of Vitamin C orally. All treatments lasted for 15 days. Twenty-four hours after the last administration, the rats were sacrificed by cervical dislocation. Blood samples and ovaries were collected for reproductive hormonal analysis, biochemical and histopathological analysis. The expressions of mRNA androgen receptor gene in the ovary were determined by real-time reverse transcriptase polymerase chain reaction. All data were analysed using one-way ANOVA. RESULTS: There was a significant decrease (p < 0.05) in the antioxidant and metabolic enzyme activity in the DHEA treated group compared with the control group. DHEA co-administration with Vitamin C showed a significant decrease in Malondialdehyde, cytokines and Estrogen and a significant increase (p < 0.05) in antioxidant and metabolic enzymes compared with DHEA treated group only. The histopathological evaluation demonstrates a reduction in cystic and atretic ovaries, increased expression of Bcl2 and E-Cadherin with a reduction in Bax expression in the group co-administered with DHEA and Vitamin C. The DHEA group showed overexpression of mRNA Androgen Receptor gene in the ovaries compared to the control group. CONCLUSION: This study shows that Vitamin C plays a protective role against DHEA-Induced Polycystic Ovary in Wistar rats via its antioxidant and anti-apoptotic mechanisms.