Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

Bisphenol A (BPA), a widely used organic synthetic chemical alters spermatogenesis and is a potential risk factor for male infertility. Diabetes-induced hyperglycemia has a negative impact on different vital organs including the testis. However, the effect of BPA on male fertility and gonadal development in diabetic (DIA) patients is unknown. This study explores the role of BPA exposure on testicular toxicity in a DIA rat. The DIA condition in male Sprague-Dawley (SD) rats (4 weeks aged) was induced with the administration of a single dose of streptozotocin (55 mg/kg ip, in cold citrate buffer pH 4.5). BPA was administered orally at the dose of 40 mg/kg/day for 4 consecutive weeks. Various endpoints of the toxicity include biochemical estimations, histological evaluations, oxidative stress parameters, DNA damage assays (apoptosis and endonuclease III), expressions of 8-hydroxy-2'-deoxyguanosine (8-OHdG), nuclear factor-erythroid 2-related factor 2 (Nrf-2), catalase, superoxide dismutase 1 (SOD-1), octamer-binding transcription factor 4 (OCT4), and Sirtulin (silent mating type information regulation 2 homolog) 1 (SIRT 1). The results confirmed that BPA exacerbated the testicular toxicity by altering several biochemical parameters, increasing oxidative stress, cellular/tissue injury, DNA damage, apoptosis, and 8-OHdG expression, while decreasing the levels of Nrf-2, catalase, SOD-1, OCT4, and SIRT1 expressions in the testes of DIA rat. Linear regression analyses indicated a positive correlation between apoptosis and 8-OHdG, OCT4, and DNA damage (nuclear diffusion factor and tail length). The present study confirmed that BPA exposure in DIA conditions exacerbated the testicular damages in SD rats. Therefore, the DIA condition might have increased male gonadal toxicity due to BPA exposure and requires further attention to maintain their normal reproductive health.