Bisphenol-A inhibits improvement of testosterone in anxiety- and depression-like behaviors in gonadectomied male mice.

Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.