Bisphenol A induces oxidative stress and decreases levels of insulin receptor substrate 2 and glucose transporter 8 in rat testis.

ABSTRACT

Bisphenol A (BPA), a monomer present in plastics, is known to impair male reproductive functions. Testis executes high-energy-demanding processes such as spermatogenesis and steroidogenesis, the successful accomplishment of which requires several factors including glucose. In this context, we sought to investigate the effects of low doses of BPA on glucose metabolism in the testis of rats and to delineate whether oxidative stress has any role to play in mediating the effects. Bisphenol A was orally administered to rats at dose levels of 0.005, 0.5, 50, and 500 µg/kg body weight for 45 days. A positive control was maintained by orally administering 17ß-estradiol at a dose of 50 µg/kg body weight. The levels of plasma glucose and insulin were significantly increased, whereas the testicular glucose level significantly decreased following exposure to BPA and estradiol. A dose-dependent increase in the level of hydrogen peroxide (H2O2) and a significant decline in the activities of hexokinase and phosphofructokinase was observed in the testis of rats treated with BPA. Western blot analyses of insulin receptor substrate 2 (IRS-2) and glucose transporter 8 (GLUT-8) in the testis showed a decline in the levels of these proteins following BPA administration. Immunolocalization of GLUT-8 protein in the testis revealed decreased expression of this protein in spermatocytes and developing spermatids of rats exposed to BPA. The results suggest that persistent exposure to low doses of BPA could disturb glucose homeostasis in the testis and thereby impair testicular functions.