Institut National de la Recherche Agronomique/Institut National Polytechnique/Université Paul Sabatire, Ecole Nationale Vétérinaire de Toulouse, Laboratoire de Physiologie, 23 chemin des Capelles, BP 87614, F-31076 Toulouse cedex 3, France.
Endocrinology. 2013 Jan;154(1):521-8. doi: 10.1210/en.2012-1401. Epub 2012 Nov 13.
The putative thyroid-disrupting properties of bisphenol A (BPA) highlight the need for an evaluation of fetal exposure and its consequence on the mother/newborn thyroid functions in models relevant to human. The goals of this study were to characterize in sheep a relevant model for human pregnancy and thyroid physiology, the internal exposures of the fetuses and their mothers to BPA and its main metabolite BPA-glucuronide (Gluc), and to determine to what extent it might be associated with thyroid disruption. Ewes were treated with BPA [5 mg/(kg · d) sc] or vehicle from d 28 until the end of pregnancy. Unconjugated BPA did not appear to accumulate in pregnant ewes, and its concentration was similar in the newborns and their mothers (0.13 ± 0.02 and 0.18 ± 0.03 nmol/ml in cord and maternal blood, respectively). In amniotic fluid and cord blood, BPA-Gluc concentrations were about 1300-fold higher than those of BPA. Total T(4) concentrations were decreased in BPA-treated pregnant ewes and in the cord and the jugular blood of their newborns (30% decrease). A similar difference was observed for free T(4) plasma concentrations in the jugular blood of the newborns. Our results show in a long-gestation species with a similar regulatory scheme of thyroid function as humans that BPA in utero exposure can be associated with hypothyroidism in the newborns. If such an effect were to be confirmed for a more relevant exposure scheme to BPA, this would constitute a major issue for BPA risk assessment.
双酚 A（BPA）假定的甲状腺干扰特性突出表明，需要在与人类相关的模型中评估胎儿暴露及其对母亲/新生儿甲状腺功能的影响。本研究的目的是在绵羊中描述一种与人类妊娠和甲状腺生理学相关的模型，评估胎儿及其母亲对 BPA 和其主要代谢物 BPA-葡糖苷酸（Gluc）的内暴露情况，并确定其与甲状腺干扰的关联程度。从第 28 天开始，母羊每天通过皮下注射（sc）接受 5mg/（kg·d）的 BPA 或载体处理，直至妊娠结束。未结合的 BPA 似乎没有在怀孕的母羊体内蓄积，其浓度在新生儿及其母亲中相似（脐带血和母血中的浓度分别为 0.13±0.02 和 0.18±0.03nmol/ml）。在羊水中和脐带血中，BPA-Gluc 的浓度比 BPA 高约 1300 倍。BPA 处理的怀孕母羊及其新生儿的脐带和颈静脉血中的总 T4 浓度降低（降低 30%）。新生儿颈静脉血中的游离 T4 血浆浓度也观察到类似的差异。我们的研究结果表明，在一种具有与人类相似的甲状腺功能调节机制的长妊娠期物种中，宫内 BPA 暴露可能与新生儿的甲状腺功能减退有关。如果这种效应在更相关的 BPA 暴露方案中得到证实，这将构成 BPA 风险评估的一个主要问题。
