PMID- 24475139 OWN - NLM STAT- MEDLINE DCOM- 20150220 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 1 DP - 2014 TI - ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR. PG - e86549 LID - 10.1371/journal.pone.0086549 [doi] LID - e86549 AB - 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 microg/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 microg/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-gamma (IFN-gamma) 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. FAU - Wu, Yanming AU - Wu Y AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. FAU - Chen, Xiao AU - Chen X AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. FAU - Zhou, Qian AU - Zhou Q AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. FAU - He, Qizhi AU - He Q AD - Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. FAU - Kang, Jiuhong AU - Kang J AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China ; Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, P.R. China. FAU - Zheng, Jing AU - Zheng J AD - Department of Ob/Gyn, University of Wisconsin, Madison, Wisconsin, United States of America. FAU - Wang, Kai AU - Wang K AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. FAU - Duan, Tao AU - Duan T AD - Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China ; Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140124 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester) RN - 0 (Angiopoietin-2) RN - 0 (Endoglin) RN - 0 (Eng protein, rat) RN - 0 (Environmental Pollutants) RN - 0 (Indoles) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Pgf protein, rat) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (Pregnancy Proteins) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 0 (Thiazoles) RN - 144589-93-5 (Placenta Growth Factor) RN - 82019-03-2 (2-hydroxy-1,3,7,8-tetrachlorodibenzo-4-dioxin) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Angiopoietin-2/genetics/metabolism MH - Animals MH - Endoglin MH - Environmental Pollutants/*toxicity MH - Female MH - Fetal Death MH - Fetus/blood supply/*drug effects/metabolism MH - Gene Expression/drug effects MH - Indoles/*toxicity MH - Interferon-gamma/genetics/metabolism MH - Intracellular Signaling Peptides and Proteins/genetics/metabolism MH - Placenta/blood supply/*drug effects/metabolism MH - Placenta Growth Factor MH - Polychlorinated Dibenzodioxins/*analogs & derivatives/toxicity MH - Pregnancy MH - Pregnancy Proteins/genetics/metabolism MH - Rats MH - Receptors, Aryl Hydrocarbon/agonists/genetics/metabolism MH - Thiazoles/*toxicity MH - Vascular Remodeling/drug effects PMC - PMC3901702 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/01/30 06:00 MHDA- 2015/02/24 06:00 PMCR- 2014/01/24 CRDT- 2014/01/30 06:00 PHST- 2013/05/06 00:00 [received] PHST- 2013/12/11 00:00 [accepted] PHST- 2014/01/30 06:00 [entrez] PHST- 2014/01/30 06:00 [pubmed] PHST- 2015/02/24 06:00 [medline] PHST- 2014/01/24 00:00 [pmc-release] AID - PONE-D-13-18508 [pii] AID - 10.1371/journal.pone.0086549 [doi] PST - epublish SO - PLoS One. 2014 Jan 24;9(1):e86549. doi: 10.1371/journal.pone.0086549. eCollection 2014.