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amphibian provides easy access to and treatment of any developmental stage,
making such vertebrate models precious tools to analyze the molecular
mechanism implied in TH signaling during embryogenesis. As we have al-
ready stated, in amphibians, plasma TH concentrations at stages earlier than
NF52 were assumed to be too low to measure ( Leloup & Buscaglia, 1977;
Regard et al., 1978 ). Analyzing morphological and biochemical data as well
as profiles of mRNA encoding the Xenopus TH receptors ( thr) , led to the
proposition that X. laevis embryos start to show competence to respond
to T 3 treatment between NF stages 40-44 ( Shi et al., 1996; Tata, 1968;
Yaoita & Brown, 1990 ). However, such studies were carried out before
the dynamics of different actors of thyroid signaling in early embryogenesis
was known and hence no studies at that time addressed whether TH target
genes were sensitive to antagonism or endocrine disruption during this
period, hence our recent reanalysis of this possibility.
5. DOES TH SIGNALING DURING EARLY DEVELOPMENT
REPRESENT A NEW SCENARIO FOR ENDOCRINE
DISRUPTION?
5.1. Epidemiological evidence for the presence of
endocrine-disrupting chemicals during the early
development
The above arguments in favor of active thyroid signaling during early
embryogenesis lead to the question of what could be the consequences
on embryogenesis of an intermittent, or even constant, exposure to xeno-
biotics with the potential to interfere with TH signaling ( Boas, Feldt-
Rasmussen, &Main, 2012; Zoeller et al., 2002 ). This question has relevance
for both human health and biodiversity. Not only the water of rivers and
lakes is increasingly polluted, threatening developing aquatic organisms
but also human amniotic fluid can contain significant amounts of environ-
mental contaminants that have TH-disrupting effects ( Cariou et al., 2008;
Kawashiro et al., 2008; Kim, Lee, Kim, & Oh, 2011; Miller, Chernyak,
Domino, Batterman, & Loch-Caruso, 2012 ). Of most concern are bromi-
nated flame retardants (BFRs) that include polybrominated diphenyl ethers
(PBDE) and tetra-bromo-bisphenol A (TBBPA). Significant levels of these
BFRs have been found in numerous human tissues and fluids, notably in ma-
ternal milk, serum, umbilical cord tissue, and cord blood ( Cariou et al., 2008;
Kawashiro et al., 2008 ). Both of these substances are known to interfere with
TH signaling.
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