Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD, an environmental toxicant) induces the intrauterine
fetal death in many species via the activation of
aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic
acid methyl
ester (ITE) and
TCDD on the
vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg
body weight (bw) ITE, 1.6 and 8.0 µg/kg bw
TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine
fetal death was observed only in 8.0 µg/kg bw
TCDD-exposed group and no significant difference was seen in either the placental weight or the
fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control,
TCDD, but not ITE, suppressed the placental
vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic
growth factors between ITE and
TCDD-exposed groups, especially
Angiopoietin-2 (Ang-2),
Endoglin,
Interferon-γ (IFN-γ) and
placenta growth factor (PIGF). These results suggest ITE and
TCDD differentially regulate the
vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in intrauterine
fetal death.