Superfund Research Program
PCBs: Metabolism, Genotoxicity and Gene Expression in vivo
Project Leader: Larry W. Robertson
Grant Number: P42ES013661
Funding Period: 2006-2020
Final Progress Reports
The goal of this Project is to identify targets and mechanisms of toxicity as a basis for understanding the risks of polychlorinated biphenyls (PCBs) to human health and their amelioration. Targets investigated include liver and bone, and especially the reproductive and developmental system. PCB126, an aryl hydrocarbon receptor (AhR) agonist and the most potent dioxin-like toxicant among the 209 PCB congeners, may play a role in the functioning of the female reproductive system. Therefore, the researchers investigated the effects of prenatal exposure to PCB126 on pregnant rats and their fetuses. Pregnant Sprague-Dawley rats (dams) received a single IP exposure to different doses of PCB126 (0, 0.2, 1, or 5 micromol/kg) on gestation day 12 and were necropsied six days later. PCB126 caused: reduced body and thymus weights; increased liver weight in dams and liver injury in the form of nonlipid cytoplasmic vacuolation in hepatocytes; and altered serum levels of some important hormones, i.e., estradiol was significantly and dose-dependently increased while leptin levels were decreased. These effects may impair fetal development and need further analysis. Additionally, PCB126 produced necrosis and increased thickness of different layers in the placenta that might cause insufficient nutrition and energy transfer to the fetuses. At the highest dose, PCB126 exposed dams showed significant adverse pregnancy outcomes which included early embryonic deaths, fetal deaths, low birth weights, and a skewed fetal sex ratio towards males. Results show that even short time in utero exposure to PCB126 impaired embryo development and produced endocrine and hepatic disruptions in pregnant dams. Further exploration of the mechanisms may enable the design of protective interventions.