Superfund Research Program
Placental-Uterine Effects of Chlorinated Hydrocarbons
Project Leader: Kathleen T. Shiverick
Grant Number: P42ES007375
Funding Period: 1995-2006
Project Summary (1995-2000)This project investigates mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) have disruptive effects on placental-uterine function. These chlorinated hydrocarbons are known to bind to the aromatic hydrocarbon receptor (AhR) and induce cytochrome P450 1A1 (AHH). However, mechanisms which underlie the utero-placental toxicity of Ah inducers remain to be elucidated. The hypothesis under study is that TCDD and PCBs alter placental-uterine functions by disrupting growth regulatory networks which are recognized to be important to placental invasiveness, proliferation and hormone secretion, as well as uterine cell growth. This research employs an in vitro model of cultured human cells and an in vivo animal model to determine endpoints which are the most sensitive biomarkers of exposure and toxicity for prototype chlorinated hydrocarbons. These studies are also identifying the cellular and molecular processes altered by TCDD and PCBs in human and rat placental-uterine tissues, respectively.