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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
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Thyroid hormone signaling in the Xenopus laevis embryo is functional and susceptible to endocrine disruption

J B Fini1, S Le Mével, K Palmier

  • 1Unité 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
|September 13, 2012
PubMed

Insights

Thyroid hormone (TH) is crucial for early brain development. Disrupting TH signaling in Xenopus embryos impacts neurogenesis and neural stem cell function, highlighting a critical window for endocrine disruption.

Area of Science:

  • Developmental Biology
  • Neuroscience
  • Endocrinology

Background:

  • Thyroid hormone (TH) is vital for vertebrate brain development, with research often focusing on perinatal stages.
  • Early human infant neuromotor development correlates with first-trimester maternal TH levels, suggesting critical roles in early embryogenesis.
  • Studying early mammalian embryogenesis is challenging, making alternative models like Xenopus laevis valuable for physiological experimentation.

Purpose of the Study:

  • To investigate the role of TH signaling in early embryonic brain development before the embryonic thyroid gland forms.
  • To characterize the expression dynamics of TH signaling components (ligands, receptors, deiodinases) during early Xenopus laevis development.
  • To assess the impact of TH disruption on neurogenesis and neural gene expression in developing Xenopus embryos.

Main Methods:

  • Detailed analysis of TH signaling components (ligands, thyroid hormone receptors (TR), deiodinases) during early Xenopus laevis development.
  • Quantification of TH levels and gene expression profiles at specific developmental stages (37-41).
  • Experimental exposure of embryos to a TH antagonist (NH-3) and a known TH disruptor (tetrabromobisphenol A) to assess effects on gene expression and cell proliferation.

Main Results:

  • Dynamic expression profiles for TH ligands, deiodinases, and TR were observed during early Xenopus development.
  • Significant increases in T(3) levels and mRNA for deiodinases and TR occurred between developmental stages 37 and 41, coinciding with neurogenesis.
  • Exposure to TH disruptors (NH-3 or tetrabromobisphenol A) modulated TH target gene expression and reduced brain cell proliferation.

Conclusions:

  • TH signaling plays a regulatory role in early neurogenesis in Xenopus laevis.
  • The early embryonic period in Xenopus represents a sensitive window for endocrine disruption by TH-modulating agents.
  • These findings underscore the importance of TH signaling in early brain development and potential risks from environmental endocrine disruptors.

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