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 remain undefined. Because parturition requires the development of oscillatory uterine contractions, this project is investigating how PCBs alter uterine muscle contraction. 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. Dichlorobiphenyls with ortho substitution of one phenyl ring stimulated contraction frequency if the other ring had a chlorine substitution at the para position, whereas 4,4'-dichlorobiphenyl had no significant effect on oscillatory uterine contractions. Studies failed to demonstrate significant membrane depolarization by 2,4'-dichlorobiphenyl using the membrane potential dye DiBAC4(3), suggesting that stimulation of uterine contraction frequency is not related to significant increase of membrane excitability. Additional studies showed that nonchlorinated biphenyl, 2'-monochlorobiphenyl and 2,2'-dichlorobiphenyl promoted desynchronization of uterine contractions. Because 2,2'-dichlorobiphenyl-induced desynchronization was reversed by antioxidants, its mechanism may involve oxidative stress. The results from these experiments may provide a scientific basis for previous reports that PCBs alter parturition.