The effect of bisphenol A on testicular steroidogenesis and its amelioration by quercetin: anin vivoandin silicoapproach

Abstract

Bisphenol A (BPA), a phenyl ring containing synthetic xenoestrogen, is widely used in the manufacture of polycarbonate plastics, epoxy resins and as a non-polymer additive to other plastics. Food is considered as the main source of exposure to BPA as it leaches out from food containers as well as surface coatings. It causes toxicity in the liver, kidney, brain, and other organs by initiating the process of lipid peroxidation. The present investigation was an attempt to evaluate the effect of BPA on steroidogenesis and its amelioration by quercetin. Inbred Swiss strain male albino mice were orally administered with 80, 120 and 240 mg per kg body weight per day of BPA for 45 days. The results revealed that BPA causes significant ( < 0.05) and dose-dependent changes in the body weight and biochemical parameters like protein, cholesterol and lipid contents as well as activities of 3β-and 17β-hydroxysteroid dehydrogenases in the testis of mice. It was also found to significantly reduce the testosterone level in serum. Oral administration of quercetin (30, 60 and 90 mg per kg body weight per day) along with a high dose of BPA (240 mg per kg body weight per day) for 45 days caused significant amelioration in the body weight and steroidogenesis as compared to the BPA alone treated group. The effect was dose-dependent. This amelioration in BPA-induced toxicity might be due to the antioxidative properties of quercetin. The reduction in the function of enzymes was confirmed by bindings. BPA and quercetin show competitive binding with steroidogenic enzymes as well as binding with each other. This could be a possible mechanism to reduce the toxic effect of BPA which has been supported by molecular dynamics simulations for molecular level recognition with structural insights.

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

“…An acetylated form of quercetin 7 Icariin (11) is a prenylated flavonol glycoside ( Figure 6) derived from kaempferol (10) and isolated from several species of plant belonging to the genus Epimedium, such as the horny goat weed. Quercetin (7), which does not have an extra hydroxyl in the position 5 of the B-cycle as in myricetin (8), has been shown to improve steroidogenesis and testosterone levels in male mice exposed to bisphenol A, widely used in the production of plastics [64]. However, the molecular mechanism responsible for such improvement may be attributable to the antioxidative properties of quercetin (7).…”

In vivo analysis of bisphenol A-induced sub-chronic toxicity on reproductive accessory glands of male mice and its amelioration by quercetin

“…Previous studies show that BPA reduces steroidogenesis in vivo and spermatogenesis (Samova et al, 2016;Samova et al, 2018). Prostate gland is androgen-dependent tissues.…”

Bisphenol A Down-Regulates The mRNA Expression of Steroidogenic Genes and Induces Histopathological Changes in Testes Of Rats

“…The reproductive toxicity of BPA was extensively studied both in vivo and in vitro in different animal species and cell lines [30][31][32][33] with wide range of doses and concentrations of BPA particularly in case of in vitro studies. Even in case of in vivo studies that used very low doses of BPA, pregnant dams or their pups were used as experimental model, meaning that the exposure to the endocrine disruptor was applied in critical periods of life [34].…”

“…Even in case of in vivo studies that used very low doses of BPA, pregnant dams or their pups were used as experimental model, meaning that the exposure to the endocrine disruptor was applied in critical periods of life [34]. But concerning to in vivo studies in adult animal species, most of them testified high doses of BPA (1 to 240 mg/kg) in adult male rats and mice [14,15,33,35]. Whereas, the current reference dose of BPA according to Environmental Protection Agency (EPA) is 50 μg/kg bw/day [36].…”