Endocrine effects of the plasticizer bisphenol A on thyroid and reproductive system during larval development of the South African clawed frog (Xenopus laevis)

In this study, the effects of the plasticizer bisphenol A (BPA) on both, the thyroid and reproductive system during the larval development of Xenopus laevis were investigated using semistatic as well as flow-through exposure systems. Neither in the semistatic nor in the flow-through exposure system BPA affected metamorphosis in this study. The analyzed parameters time course of completion of metamorphosis, developmental stage, whole body length, hind limb length and TSHß-mRNA expression remained unaffected by BPA after long-term exposure whereas both, body weight and length were significantly increased already by 10-8 M BPA using the flow-through system. Only moderate anti-thyroidal effects on the TH-dependent gene expression were found after short-term exposure. In X. laevis tadpoles BPA significantly inhibited the T3-induced mRNA expression after 24, 48, and 72 hours for TRß and after 48 hours for BTEB. Thus, BPA seems to have only a moderate impact on receptor-mediated processes in target cells. BPA did not affect the sex ratio in metamorphosed froglets. On the histological level oogonia and lacunae were found in testes already for the lowest BPA concentration of 10-9 M. Similar features were observed in males treated with E2. Thus, clearly evidences for feminization were found for BPA in this study. Furthermore, E2 and the highest BPA concentration of 10-6 M significantly inhibited ARO-mRNA expression in brain of metamorphosed froglets but only BPA inhibited FSHß-mRNA expression additionally. LHß-mRNA remained at control levels in all treatments. BPA did not affect the sex dimorphic gene expression of ARO-, Follst-, Sox9-, Dhh-, and Dmrt1-mRNA in gonads of NF stage 57 tadpoles and metamorphosed froglets. In contrast, hepatic gene expression of VTG and IGF-1 were enormously altered by BPA in metamorphosed froglets. 10-6 M BPA dramatically increased VTG-mRNA expression in both, males and females; whereas lower BPA concentrations tested expressed VTG-mRNA levels as low as found in the negative control. IGF-1-mRNA expression was significantly increased by BPA in males but not in females. Especially the low dose effects on liver and gonads found in metamorphosed frogs are alarming because 10-9 M and 10-8 M BPA tested are concentrations of environmental relevance.