Evidence for bisphenol A-induced disruption of maternal thyroid homeostasis in the pregnant ewe at low level representative of human exposure.

Many uncertainties remain regarding the potential of bisphenol A (BPA) as a thyroid disruptor in mammals and the relevance of experimental data to humans. The relevance of the exposure schemes used in experimental in vivo studies is also a major source of uncertainty when analysing the risk of BPA exposure for human health. In this context, the goals of our study, conducted in an ovine model relevant to human gestation and thyroid physiologies, were to: 1) determine the equivalence of subcutaneous and dietary exposures and 2) determine if environmentally relevant doses of BPA can alter gestational and newborn thyroid functions. The difference between the two routes of exposure was mainly related to the overall BPA exposure and much less to the peak serum concentrations. Interestingly, BPA-GLUC (the main metabolite of BPA) internal exposure via both routes was almost identical. The decrease in thyroid hormones concentration overtime was more accentuated in ewes treated with BPA, particularly with the medium dose (50 μg/(kg.d); SC) for which the maximum BPA concentrations were predicted to be within the 1-10 ng/mL range i.e. very similar to the highest blood concentrations reported in humans. The balance between TT4 and rT3 varied differently between the vehicle and the medium dose group. The mechanisms underlying those modifications of maternal thyroid homeostasis remain to be determined. Our study did not evidence significant modification of TSH secretion or binding to serum proteins but might suggest an effect at the level of deiodinases.