title: Thyroid hormone signaling in the Xenopus laevis embryo is functional and susceptible to endocrine disruption.
abstract: 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.
authors.affiliation: 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.
authors.forename: J B
authors.initials: JB
authors.lastname: Fini
authors.forename: S
authors.initials: S
authors.lastname: Le Mével
authors.forename: K
authors.initials: K
authors.lastname: Palmier
authors.forename: V M
authors.initials: VM
authors.lastname: Darras
authors.forename: I
authors.initials: I
authors.lastname: Punzon
authors.forename: S J
authors.initials: SJ
authors.lastname: Richardson
authors.forename: M S
authors.initials: MS
authors.lastname: Clerget-Froidevaux
authors.forename: B A
authors.initials: BA
authors.lastname: Demeneix
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D010642:Phenoxyacetates / Q000494:pharmacology*; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013961:Thyroid Gland / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C461658:(4-(4-hydroxy-3-isopropyl-5-(4-nitrophenylethynyl)benzyl)-3,5-dimethylphenoxy)acetic acid; D052244:Endocrine Disruptors; D010642:Phenoxyacetates; D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; C020806:tetrabromobisphenol A