Dietary Zinc Deficiency Increases Bisphenol A Toxicity in Diabetic Rat: Studies on the Testicular and Epididymal Pathophysiology

Abstract

Bisphenol A (BPA), an endocrine disrupter extensively used in plastics products, that causes male reproductive dysfunction in humans and experimental systems. Type 1 diabetes (T1D) associates hyperglycaemia dysregulate the spermatogenesis and antioxidant status in the testes, which negatively impact on male fertility in adults. Dietary zinc (Zn) deficiency is a global health concern, because majority of the individuals are suffering from certain range of Zn‐deficiency. Zn plays an important role in the regulation and maintenance of testicular physiology and the overall reproductive health. The present study was aimed to investigate the influence of Zn‐deficiency on BPA induced germinal cell and male gonadal toxicity in diabetic rat. Sprague Dawley rats (4 weeks old) were randomly divided into eight different groups; like control (standard pellet diet and aquapure drinking water), BPA (10 mg/kg/day), Zn‐deficient diet (ZDD; Zn‐deficient diet), diabetic (DIA), BPA+ZDD, BPA+DIA, ZDD+DIA and BPA+ZDD+DIA for four weeks. Diabetes was induced by injecting single dose of streptozotocin (55 mg/kg) freshly prepared in cold citrate buffer at pH 4.5. The evaluation of various end‐points such as assessment of body and organ weights, biochemical estimations, sperm parameters. testes and epididymis histopathology, quantification of testicular DNA damage and sperm apoptosis were conducted. Testicular 8‐OHdG immunoexpression as well as catalase and OCT4 expressions were carried out by western blot analysis. The results showed that dietary Zn‐deficient condition significantly increased the BPA toxicity by decreasing body and organ weight, serum albumin and increasing glucose, SGPT, SGOT and BUN significantly in diabetic condition. Further, significant decrease in sperm count, sperm motility and increase in sperm deformities were observed. The Zn‐deficiency significantly increased the BPA induced testicular and epididymal tissue injury, elevated testicular 8‐OHdG immunoexpression and sperm apoptosis in diabetic rat. Moreover, BPA exposure significantly decreased the testicular catalase and OCT4 expressions in dietary Zn‐deficient diabetic rat. The present results concluded that dietary Zn‐deficiency exacerbated the BPA induced gonadal toxicity by hypogonadism, increased sperm abnormalities, testicular and epididymal cellular damage, testicular DNA damages, sperm apoptosis as well as decreased the testicular catalase and OCT4 expressions in diabetic rat.