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3.2. Effects/mechanism of EDC action
3.2.1 BPA
BPA has well-known estrogenic effects, but BPA also affects brain differen-
tiation, a process not known to be strongly influenced by estrogen ( vom Saal
& Hughes, 2005 ). TH, on the other hand, is critical for proper brain devel-
opment, opening the possibility that BPA may be a TH endocrine disruptor
as well. Indeed, BPA inhibited TH-induced external morphological changes
as well as intestinal remodeling ( Heimeier, Das, Buchholz, & Shi, 2009 ).
The effect of BPA on established TH-response genes was to partially block
induced changes. To examine effects of BPA on transcription across all
genes, tadpoles were treated with 2 nM TH, 10 m M BPA, or both together
for 4 days and then a microarray analysis was carried out on the intestine.
Genes regulated by TH and TH
BPA compared to controls were relatively
similar, despite the general inhibition of BPA on metamorphic transforma-
tion. However, because BPA only partially inhibited TH-induced changes
in gene regulation, it is possible that BPA attenuates but does not abolish
TH-response gene induction. Thus, when comparing gene sets from TH
versus TH
þ
BPA, BPA inhibited regulation either up or down in 501
genes, more than 50% of which were TH-response genes. Because BPA re-
duced most TH-induced gene regulation, BPA likely blocks TH-dependent
metamorphosis via inhibition of most if not all molecular and developmental
pathways required for metamorphosis.
þ
3.2.2 Atrazine
Atrazine has negative effects on growth, metabolism, immune function, and
sexual differentiation in fish and frogs ( Hayes, 2005 ). However, the molec-
ular mechanisms underlying these organismal phenotypes are not well un-
derstood. To better understand how atrazine interacts with the organism at
the level of gene expression, Ide and colleagues carried out a microarray
analysis of tadpoles chronically exposed to 400 ppb atrazine from hatching
to climax of metamorphosis ( Langerveld, Celestine, Zaya, Mihalko, & Ide,
2009 ). This atrazine treatment throughout the larval period affected growth,
development, and survival. Fat bodies were also reduced in both male and
female tadpoles. Microarray analysis fromwhole bodies identified changes in
males (44 genes) and females (77 genes) at metamorphic climax, with less
than 50% overlap among sexes. The genes identified were involved in
growth and metabolism genes, proteolysis, fibrinogen complex formation,
and immune system function. Reproductive function genes were not
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