International Journal of Marine Science 2016, Vol.6, No.4, 1-12
10
involved in cardiac chamber formation. In the present
study, the expression of NKx2.7 and hand2 is
significantly declined in 4-t-OP exposed zebrafish at
48 and 72 hpf; however expression of Nkx2.5 without
significant difference. This result potentially indicated
the 4-t-OP induced incomplete looping of ventricle
and atrium, and chamber shape through suppressing
Nkx2.7 and hand2 expression. GATA family act
important transcription factors for the development of
diverse tissues. Tbx2 encodes a T box factor is
required for regulating heart chamber development.
Report has demonstrated that two genes, tbxa and tbxb,
were retained in zebrafish and both are required for
the development of atrioventricular canal (ACV)
(Sedletcaia and Evans, 2011). Study also report that
homozygous mutation of tbx5a gene in zebrafish leads
to defects in cardiac looping morphogenesis (Parrie et
al., 2013). The three members of GATA family,
transcription factor GATA-4, -5, and GATA-6 play a
critical role for heart development. GATA-5 is
specifically expressed in endocardium and GATA-4
and -6 are present in the myocardium. GATA-5 and
GATA-6 involved in regulating endocardial and
myocardial cell differentiation (Heicklen et al., 2005).
GATA-4 is required for heart tube formation and
ventral morphogenesis (Molkentin et al., 1997). In the
present study, the expression of tbx2a, tbx2b, tbx5a,
gata-4, -5 and -6 is significantly declined in zebrafish
exposure to 4-t-OP at 48 and 72 hpf suggesting that
4-t-OP suppresses the expression of these critical
transcription factors and leads to defects in
development and morphogenesis of heart chamber
formation. Fibroblast growth factors (FGFs) are
considered as important angiogenic factors for
vascular development (Javerzat et al., 2002).Other
investigators have demonstrated that FGF signaling
affects vascular outgrowth and is required for the
maintenance of blood vessel integrity in zebrafish (De
Smet et al., 2014). In addition to FGF, GATA-4 has
been demonstrated to regulate development of the
caudal vascular plexus in zebrafish through the
chemokine sdf1a mediation (Torregroza et al., 2012).
The present result showed that downregulation of
EGF and GATA-4 expression in the presence of
4-t-OP suggesting 4-t-OP may suppress EGF and
GATA-4 expressions in zebrafish resulting in the
absence of intersegmental vessel and parachoral vessel
and links in the caudal vein.
In conclusion, the present study is the first report
representing that the exposure of zebrafish embryos to
4-t-octylphenol resulting in highly incidence of
cardiovascular defects. The presence of 4-t-OP in
zebrafish embryos that induced expression level of
ERα and ERβ2 suggesting the 4-t-OP mimicking
estrogen which act highly binding affinity with both
ER. The 4-t-OP exposed zebrafish embryos resulted in
suppression of transcription factor NKX2.7, hand2,
Tbx2, Tbx5, FGF, GATA-4, -5 and -6 expression may
be the cause of cardiovascular defects. The
susceptibility of zebrafish model exposed to 4-t-OP
during early life suggests its role in injuring
cardiovascular development and function, which is a
health-risk concern of early life exposure in humans.
Acknowledgment
We thanks the Taiwan Zebrafish Core Facility at
Academia Sinica (TZACS), which is supported by
grant NSC 103-2321-B-001-050 from the Ministry of
Science and Technology (MOST) in Taiwan for
providing AB strain zebrafish and tansgenic zebrafish
Tg(fil-1:EGFP). This research was supported by a
grant NSC 102-2313-B-02-015 from the Ministry of
Science and Technology.
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