UBC Theses and Dissertations
Effect of genistein on the expression of testicular steroidogenic and drug-metabolizing enzymes in adult male Sprague-Dawley rats Chung, Haeun
There is increasing concern that human exposure to endocrine disruptors with estrogenic activities can adversely affect male reproductive health. Genistein is a plant-derived xenoestrogen that exhibits the ability to bind to estrogen receptors. Humans are exposed to genistein through the consumption of soybeans and processed soy products. The present study aims to investigate on the effect of genistein on the expression of testicular steroidogenic and drug-metabolizing enzymes. Thirty-seven adult male Sprague-Dawley rats were randomized into 6 groups and received vehicle (10%DMSO/90%PEG-400, v/v), genistein at 4, 40 or 400 μmol/kg/day, bisphenol A (BPA) at 200 μmol/kg/day or 17β-estradiol benzoate (EB) at 0.4 μmol/kg/day, subcutaneously, for 14 days. One day after the last treatment, rats were killed, their liver and testes were immediately excised and weighed, and the blood was collected. Body weight gain during the treatment period and serum testosterone levels were measured. Expression of CYP1B1, CYP2A1, CYP17A1, microsomal epoxide hydrolase (mEH), CYP oxidoreductase (POR), and 3β-hydroxysteroid dehydrogenase (HSD3β) in testicular microsomes was determined by immunoblot analysis. Histological examination of testis was performed by immunohistochemical analysis and H&E staining. The results showed that treatment with genistein did not affect body weight gain but treatment with BPA or EB decreased body weight gain relative to the vehicle-treated group. Liver and testis weights and serum testosterone levels were unaffected by treatment with genistein, BPA or EB. Testicular protein levels of CYP2A1, CYP17A1 and mEH but not HSD3β were decreased following treatment with genistein at 40 or 400 μmol/kg/day, BPA at 200 μmol/kg/day or EB at 0.4 μmol/kg/day. Testicular POR expression was decreased at the highest dosage of genistein (400 μmol/kg/day), BPA or EB. Testicular CYP1B1 protein levels appeared to decrease in response to treatment with genistein or BPA, but the differences, when compared to vehicle group, were not statistically significant. The testicular CYP1B1 protein level was reduced following treatment with EB. No histological changes were seen in testis regardless of the treatment given. In summary, genistein selectively suppressed expression of testicular CYP2A1, CYP17A1, mEH and POR enzymes without altering the histology of testis in adult male rats.
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