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Evaluation of Placentation and the Role of the Aryl Hydrocarbon Receptor Pathway in a Rat Model of Dioxin Exposure
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2021-11-8 , DOI: 10.1289/ehp9256
Khursheed Iqbal 1, 2 , Stephen H Pierce 1, 2 , Keisuke Kozai 1, 2 , Pramod Dhakal 1, 2 , Regan L Scott 1, 2 , Katherine F Roby 1, 3 , Carrie A Vyhlidal 1, 4, 5, 6 , Michael J Soares 1, 2, 5, 7
Affiliation  

Abstract

Background:

Our environment is replete with chemicals that can affect embryonic and extraembryonic development. Dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are compounds affecting development through the aryl hydrocarbon receptor (AHR).

Objectives:

The purpose of this investigation was to examine the effects of TCDD exposure on pregnancy and placentation and to evaluate roles for AHR and cytochrome P450 1A1 (CYP1A1) in TCDD action.

Methods:

Actions of TCDD were examined in wild-type and genome-edited rat models. Placenta phenotyping was assessed using morphological, biochemical, and molecular analyses.

Results:

TCDD exposures were shown to result in placental adaptations and at higher doses, pregnancy termination. Deep intrauterine endovascular trophoblast cell invasion was a prominent placentation site adaptation to TCDD. TCDD-mediated placental adaptations were dependent upon maternal AHR signaling but not upon placental or fetal AHR signaling nor the presence of a prominent AHR target, CYP1A1. At the placentation site, TCDD activated AHR signaling within endothelial cells but not trophoblast cells. Immune and trophoblast cell behaviors at the uterine–placental interface were guided by the actions of TCDD on endothelial cells.

Discussion:

We identified an AHR regulatory pathway in rats activated by dioxin affecting uterine and trophoblast cell dynamics and the formation of the hemochorial placenta. https://doi.org/10.1289/EHP9256



中文翻译:

二恶英暴露大鼠模型中芳基烃受体途径的定位和作用评估

摘要

背景:

我们的环境充满了会影响胚胎和胚胎外发育的化学物质。二恶英,例如 2,3,7,8-四氯二苯并-p-二恶英 (TCDD) 是通过芳烃受体 (AHR) 影响发育的化合物。

目标:

本研究的目的是检查 TCDD 暴露对妊娠和胎盘的影响,并评估 AHR 和细胞色素 P450 1A1 (CYP1A1) 在 TCDD 作用中的作用。

方法:

在野生型和基因组编辑的大鼠模型中检查了 TCDD 的作用。使用形态学、生化和分子分析评估胎盘表型。

结果:

TCDD 暴露会导致胎盘适应,如果剂量较高,则会导致妊娠终止。宫内深部血管内滋养层细胞侵袭是对 TCDD 的一个重要的胎盘位点适应。TCDD 介导的胎盘适应依赖于母体 AHR 信号传导,但不依赖于胎盘或胎儿 AHR 信号传导,也不依赖于显着的 AHR 靶标 CYP1A1 的存在。在胎盘植入部位,TCDD 激活内皮细胞内的 AHR 信号传导,但不激活滋养层细胞内的 AHR 信号传导。子宫胎盘界面的免疫和滋养层细胞行为受到 TCDD 对内皮细胞的作用的指导。

讨论:

我们确定了二恶英激活大鼠的 AHR 调节途径,影响子宫和滋养层细胞动力学以及血绒质胎盘的形成。https://doi.org/10.1289/EHP9256

更新日期:2021-11-08
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