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the liganded receptor during this period remains to be determined. How-
ever, the expression patterns of deiodinases can be used to derive hypothesis
as to which tissues may be sites of THmetabolism and action in the embryo.
For instance in neurogenic areas of stage NF 35-37
X. laevis
tadpoles, not
only are deiodinases expressed but also one or several isoforms of TRs are
expressed (see
Table 13.1
). Taking such data into account, we hypothesize
that in
Xenopus
, TH signaling plays a role in neurogenesis and in the early
formation of sensory organs (eye, ear, and olfactory system) as well as car-
tilage. In these organs, the expression patterns of the different components
are highly dynamic, suggesting very precise windows of action for TH sig-
naling, as described for retinoic acid.
The functionality of liganded TR is however difficult to analyze as TH
levels in embryos are hard to manipulate. The most straightforward treat-
ment, that of adding exogenous T
3
, can be directly neutralized and
counteracted by local D3-mediated deiodination, even in the external de-
veloping models, such as zebrafish and
Xenopus
. Despite this limitation, these
small model organisms remain more flexible models than mammalian sys-
tems, as besides the fact that there is no need for surgery to access them, there
is, moreover, no maternal influence in TH content during embryogenesis
and the amount of TH present in the egg can be evaluated. Moreover,
the analysis of TH signaling function during embryogenesis will provide
new insight into understanding how endocrine disruptors affect embryonic
development (
Fig. 13.2
).
Finally, several major endocrine disruptors have been shown not only to
interfere with TH signaling but also to be present at significant levels in the
general environment and specifically in the fetal environment. It is, how-
ever, important to remember that a given endocrine disruptor may affect
more than one endocrine pathway thus affecting multiple developmental
Figure 13.1 The different components of TH signaling pathway are present during
embryogenesis. (A) The general consensus on TH signaling is that T
3
is the key trigger
and orchestrator of amphibian metamorphosis. Nevertheless, it is also crucial for adult
physiology. TH role during embryogenesis is less defined. Whereas seric concentrations
are well known inmetamorphic and postmetamorphic tadpoles, they are irrelevant in em-
bryos. We therefore reported whole body data. (B) The analysis of T
3
and T
4
availability in
regard with TRs expression shows that when the receptors are expressed during embryo-
genesis, T
3
is present in (some) tissues. T
3
is therefore likely to bind TRs locally. (C)
Deiodinases are expressed in some tissues from early development. They can be respon-
sible for the slight T
3
increase and T
4
decrease during the first phases of embryogenesis (up
toNF45). The increase inT
4
contentbetweenNF45andNF46 indicatesdenovoTHsynthesis.
Schematic view, adapted from
Fini,LeMével,etal.(2012)
.
