SAT-203 Gestational Bisphenol A Exposure Induces Inflammatory, Oxidative Stress and Lipotoxic Changes in the Placenta of Female Sheep

Widespread exposure to environmental endocrine disrupting chemicals (EDC) has been attributed in part to the rise in non-communicable diseases. Pregnant women and their developing fetuses are vulnerable to exposure from EDC leading to adult onset disorders in the offspring in accordance with the developmental origin of health and disease (DOHAD) hypothesis. Bisphenol A (BPA) is one such EDC with estrogenic, anti-androgenic, and metabolism disrupting properties. BPA has been detected in >90% of US population. Gestational BPA exposure has been found to be associated with low birth weight, a risk factor for adult onset diseases in both human and sheep. The low birth weight may be the consequence of reduced placental efficiency stemming from disruption in inflammatory, oxidative stress and metabolic homeostasis, such as that reported in pregnancies accompanying maternal obesity and gestational diabetes. We hypothesized that gestational BPA treatment at environmentally relevant levels leads to placental inflammation, oxidative stress and lipid accumulation during early pregnancy accounting for the poor birth outcome observed. Gestational day 65 placentae were collected from pregnant Suffolk treated with 0.5mg/kg/day BPA sc starting from day 30 of gestation. Controls received equal volume of corn oil (vehicle).This BPA dose produces 1.6 ng/mL BPA concentration in the umbilical artery, levels close to that observed in the maternal circulation in US. Inflammatory markers and antioxidant expression were determined by real time RT-PCR, byproducts of lipid peroxidation (index of oxidative damage) measured using thiobarbituric acid reactive substances (TBARS) assay, and lipid accumulation as an index of lipotoxicity by oil red O staining. Data were analyzed by Student’s t-test and Cohen’s effect size analysis. Prenatal BPA treatment induced a significant (p < 0.05) increase in antioxidants glutathione reductase, and superoxide dismutase 1 and 2. While Cohen’s effect size analysis showed (1) large magnitude increase in macrophage marker CD68 and medium magnitude increase in proinflammatory cytokines chemokine ligand 2 and interleukin 1 beta; (2) large magnitude increase in TBARS, and (3) medium magnitude increase in oil red O staining in placenta from prenatal BPA. These preliminary findings indicate that gestational BPA exposure induces early disruptions in placental milieu via increased inflammation, oxidative stress and lipid accumulation. The increase in antioxidant expression evidenced in placentae of prenatal BPA treated sheep may reflect a compensatory response to overcome the oxidative stress state. The altered placental milieu may lead to reduced placental efficiency thus contributing to the low birth weight and the cardio-metabolic defects seen in prenatal BPA-treated sheep. Supported by NIH ES-016541.