Objective: 

Bisphenol A (BPA) is a plasticizer and has been extensively used in consumer products. BPA can leach from food and beverage containers, and some dental sealants and composites under normal conditions of use and enter into the human body. It has been suggested that BPA can act an endocrine disrupter in various experimental models. In the present study, we have evaluated the effects of BPA on female reproductive system by using uterotrophic assay. In addition, possible effects of BPA on the regulation of related factors including, kisspeptin, GPR54 and ERK-1/2 expression were analyzed in the brain.

Methods: 

Twenty day-old immature female Sprague-Dawley rats were selected and divided into four groups and treated with (n=6/group) vehicle (0.1 ml corn oil, sc), oestradiol (E₂, 100 mg/kg), BPA (1 mg/kg) and BPA (10 mg/kg) for three consecutive days. Twenty-four hours after last treatment, the animals were decapitated and uterus tissue was harvested for the uterotrophic assay. The brains were dissected and processed for the analysis of kisspeptin, GPR54 expressions and ERK-1/2 phosphorylation by Western blotting and immunohistochemistry.

Results: 

E₂ significantly increased the ratio of uterine weight to the body weight compared to the control group. Although this ratio was slightly raised by BPA administration, the changes were not statistically significant. E2 and BPA treatments significantly increased kisspeptin, GPR54 expression and ERK-1/2 phosphorylation in the brain at the level of hypothalamus.

Conclusions: 

The present results indicate for the first time that BPA stimulates kisspeptin and GPR54 expression in the hypothalamus of immature female rats. These findings suggest that BPA may exert estrogenic effects on the brain even before its significant impact on the uterine tissue.