Juvenile exposure to bisphenol A promotes ovarian differentiation but suppresses its growth - Potential involvement of pituitary follicle-stimulating hormone

Abstract

Bisphenol A (BPA), a plastic monomer and plasticizer, is commonly used in plastics industry, and it has been well documented to be an estrogenic endocrine disrupter. In the present study, we investigated the effect of early (juvenile) exposure to BPA on the hypothalamic-pituitary-gonad (HPG) axis in the zebrafish. Estradiol (E2) and testosterone (T) were also included as positive and negative controls respectively. Juvenile zebrafish were exposed to BPA (1 and 10μM), E2 (10nM) and T (10nM) from 20 to 40 dpf (days post-fertilization), the period of sex/gonadal differentiation, followed by histological and expression analyses at 40 dpf. The ovary and hepatic proteomes were also analyzed by mass spectrometry. Our results showed that 20day exposure to BPA and E2 increased the ratio of females; however, they both significantly suppressed ovarian growth. Meanwhile, BPA and E2 significantly suppressed fshb but stimulated lhb expression in the pituitary. These effects did not seem to involve the hypothalamus because neither BPA nor E2 altered the expression of kiss1, kiss2, gnrh2 and gnrh3 in the hypothalamus. At the ovary level, BPA and E2 both decreased lhcgr expression. Interestingly, E2 and BPA displayed different effects in the liver. E2 induced a significant hepatic hypertrophy; however, BPA had no such effect. Analysis of hepatic proteomes revealed distinct protein profiles in the E2 group as compared with the others, especially fructose-bisphospahte aldolase B. These results indicated that BPA has estrogenic effects on female reproduction, but it does not mimic all E2 actions. Our data in the zebrafish suggest that sex differentiation involves estrogens and it is a sensitive window for evaluating estrogenic activities of compounds and their impacts on wildlife reproduction.

Keywords: Bisphenol A; Estradiol; Gonadal differentiation; Ovary; Zebrafish.