Uterine muscle as a potential target of polychlorinated biphenyls during pregnancy

Because of their once-popular commercial uses, improper disposal and environmental persistence, polychlorinated biphenyls (PCBs) are common environmental contaminants found in many designated Superfund sites. Several epidemiology studies associated PCB exposure with decreased length of gestation. Recent laboratory studies, described in this review, examined PCB actions in uterine muscle in order to investigate mechanisms by which PCBs may stimulate early onset of parturition. Because increased frequency, force and coordination of oscillatory uterine contractions are the defining characteristics of parturition, the laboratory studies used uterine muscle tissue and cells to study PCB actions on uterine contraction. Acute in vitro exposures to commercial PCB mixtures and microbially dechlorinated commercial PCB mixtures increased the frequency of spontaneous oscillatory contractions of uteri from pregnant rats. Increased uterine stimulation was observed with PCB mixtures containing increased abundance of lesser-chlorinated, ortho-substituted congeners. Similarly, in vitro exposures to PCB congeners increased the frequency of spontaneous uterine oscillatory contractions in a structurally related manner, with ortho-substitution of four or fewer chlorines associated with increased stimulation. Moreover, inhibitors of phospholipase A2 prevented stimulation of oscillatory uterine contractions by the commercial PCB mixture Aroclor 1242, suggesting involvement of arachidonic acid in the Aroclor 1242-induced stimulation. Acute exposure to a hydroxylated estrogenic PCB inhibited uterine contraction acutely, but a 42-h exposure increased uterine sensitivity to the uterotonic hormone oxytocin in a manner similar to 17 beta-estradiol, suggesting an estrogenic mechanism by which some PCBs could decrease gestation length. These studies show that PCBs stimulate uterine contraction in vitro, providing biologically plausible mechanisms in support of previous epidemiology findings associating PCB exposure with decreased gestation length. Further conclusions regarding human health should be considered in the context of human exposure and the experimental limitations of the in vitro studies.