Superfund Research Program
PCB Effects on Uterine Muscle
Project Leader: Rita Loch-Caruso (University of Michigan)
Grant Number: P42ES004911
Funding Period: 1995 - 2006
Polychlorinated biphenyls (PCBs) are widespread environmental contaminants. Although previous epidemiological and laboratory animal studies indicate that some PCBs alter gestation length, the mechanisms that mediate PCB effects on parturition are unknown. This project is examining three specific hypotheses that aim to improve understanding of how polychlorinated biphenyls (PCBs) alter uterine contraction.
The first hypothesis is that stimulatory PCBs increased uterine membrane excitability through actions on ion channels that promote increased intracellular calcium concentration. The second hypothesis is that stimulatory PCBs increase contraction frequency by selectively increasing the excitability of a subpopulation of uterine smooth muscle cells that may be the pacemakers of the uterus. The third hypothesis is that inhibitory PCBs decrease the force and promote desynchronization of uterine contractions by oxidative stress-mediated inhibition of myometrial gap junctions. For each hypothesis, relationships between biochemical, cellular, tissue and whole animal responses will be analyzed.
Recent studies showed that removal of chlorines by bacteria produced PCB mixtures with increased stimulatory activity in the uterus compared with the parent non-dechlorinated mixtures. Additional studies with individual congeners suggest that the chlorine substitution pattern determines uterine activity. Uterine stimulatory activity appears to require arachidonic acid release but not protein kinase C activation By increasing our understanding of PCB actions in the pregnant uterus, the results from these experiments will contribute to improved assessment of risk to pregnant women and may provide a scientific basis for previous reports that PCBs alter parturition.