Impairment in protein expression profile of testicular steroid receptor coregulators in male rat offspring perinatally exposed to Bisphenol A

Aims: Steroid hormones and steroid receptors (SRs) play a crucial role in spermatogenesis. Steroid receptor coregulators are the major determinants of SR functioning, and any alteration in their expression is known to be associated with impaired spermatogenesis. Since Bisphenol A (BPA) exposure leads to an impairment of spermatogenesis, we hypothesized that this effect could be associated with the altered expression of steroid receptors and their coregulators in the testes. The present study describes the effect of perinatal exposure of rats to BPA on the expression profile of testicular steroid receptor coregulators in the F-1 generation. These effects were further studied in the F-2 and F-3 generations to determine vertical transmission. Main methods: Pregnant female rats (F-0) were gavaged daily with BPA (1.2 and 2.4 mu g/kg bw) (or vehicles for controls) from gestation day 12 through postnatal day (PND) 21 to obtain the F-1 and subsequent F-2 and F-3 generations. Immunohistochemical localization of steroid receptor coactivator-1 (SRC-1), G-receptor integrating protein-1 (GRIP-1), p300/CBP/cointegrator-associated protein (p/CIP) and nuclear corepressor (NCoR) was carried out in the testes of F-1, F-2 and F-3 generation adult rats. Key findings: A significant reduction in the expression of SRC-1 and NCoR, with a parallel increase in the expression of p/CIP and GRIP-1, was observed in the testes of rats exposed perinatally to BPA. Surprisingly, a similar pattern was observed in the testes of F-2 and F-3 rats. Significance: Perinatal exposure of male rats to BPA leads to transgenerational perturbations in the expression profile of testicular steroid receptor coregulators. (C) 2009 Elsevier Inc. All rights reserved.