Genetic stress (IL-10 deficiency) and toxicant (PCB)-induced disruption of pregnancy



Several epidemiologic studies have provided evidence that a significant number of pregnant women living within the World Trade Center disaster area experienced a high rate of low birth weight and premature deliveries. Our hypothesis is that these women were predisposed to pregnancy disruption effects of toxicants detected in the dust of the disaster area. We sought to examine the effects of PCB on pregnancy outcome in an IL-10-/- mouse model. IL-10-/- or congenic wild type mice of 6–8 weeks age were given i.p injections of Aroclor 1254 (PCB) at doses of 50 or 500 μg/mouse in 100 μL corn oil on gestational day (gd) 1 and 7 or an equivalent (100 μL) amount of corn oil. Mice were sacrificed on gd 13 and uteri and spleen were excised and collected. Uterine mononuclear cells (UMC) and splenic mononuclear cells (SMC) were isolated. These cell populations were subjected to phenotypic and functional characterization. A portion of uterine tissue was either snap frozen for placental PCB contents or for histology. No doses of Aroclor 1254 affected the pregnancy outcome in wild type mice. However, IL-10-/- mice experienced fetal resorption when injected with high dose (500 μg/mouse) of Aroclor 1254. Local immune dysregulation and placental anomalies including apoptosis and immunocyte infiltration are currently being investigated. Our results strongly suggest that IL-10 deficiency and PCB-mediated immunotoxicity lead to adverse pregnancy outcomes.

Acknowledgement:  Supported by NIEHS Superfund Basic Research Program Award P42ES13660.