Unité Mixte de Recherche Centre National de la Recherche Scientifique 7221, Evolution des Régulations Endocriniennes CNRS UMR 7221/Muséum National d'Histoire Naturelle Département Régulations, Développement et Diversité Moléculaire, 75231 Paris, France.
Endocrinology. 2012 Oct;153(10):5068-81. doi: 10.1210/en.2012-1463. Epub 2012 Sep 11.
Thyroid hormone (TH) is essential for vertebrate brain development. Most research on TH and neuronal development focuses on late development, mainly the perinatal period in mammals. However, in human infants neuromotor development correlates best with maternal TH levels in the first trimester of pregnancy, suggesting that TH signaling could affect early brain development. Studying TH signaling in early embryogenesis in mammals is experimentally challenging. In contrast, free-living embryos, such as Xenopus laevis, permit physiological experimentation independent of maternal factors. We detailed key elements of TH signaling: ligands, receptors (TR), and deiodinases during early X. laevis development, before embryonic thyroid gland formation. Dynamic profiles for all components were found. Between developmental stages 37 and 41 (~48 h after hatching, coincident with a phase of continuing neurogenesis) significant increases in T(3) levels as well as in mRNA encoding deiodinases and TR occurred. Exposure of embryos at this developmental stage for 24 h to either a TH antagonist, NH-3, or to tetrabromobisphenol A, a flame retardant and known TH disruptor, differentially modulated the expression of a number of TH target genes implicated in neural stem cell function or neural differentiation. Moreover, 24-h exposure to either NH-3 or tetrabromobisphenol A diminished cell proliferation in the brain. Thus, these data show first, that TH signaling exerts regulatory roles in early X. laevis neurogenesis and second, that this period represents a potential window for endocrine disruption.
甲状腺激素 (TH) 对脊椎动物大脑发育至关重要。大多数关于 TH 和神经元发育的研究都集中在后期发育上，主要是哺乳动物的围产期。然而，在人类婴儿中，神经运动发育与妊娠早期的母体 TH 水平相关性最好，这表明 TH 信号可能会影响早期大脑发育。在哺乳动物中研究早期胚胎发生中的 TH 信号是具有实验挑战性的。相比之下，自由生活的胚胎，如非洲爪蟾，允许在不依赖母体因素的情况下进行生理实验。我们详细介绍了 TH 信号在非洲爪蟾早期发育过程中的关键要素：配体、受体 (TR) 和脱碘酶，这些都是在胚胎甲状腺形成之前。发现所有成分都有动态分布。在发育阶段 37 到 41 之间（孵化后约 48 小时，正好是神经发生持续的阶段），T3 水平以及编码脱碘酶和 TR 的 mRNA 水平显著增加。在这个发育阶段，将胚胎暴露于 TH 拮抗剂 NH-3 或阻燃剂和已知的 TH 破坏剂四溴双酚 A 24 小时，可差异调节许多与神经干细胞功能或神经分化相关的 TH 靶基因的表达。此外，NH-3 或四溴双酚 A 暴露 24 小时会减少大脑中的细胞增殖。因此，这些数据表明，首先，TH 信号在早期非洲爪蟾神经发生中发挥调节作用，其次，这段时期代表了内分泌干扰的潜在窗口。
