OR06-02 Placental Distribution Of Polybrominated Diphenyl Ethers (Pbdes) And Thyroid Hormones Across Gestation In PBDE-exposed Wistar Rats

Abstract

Abstract Disclosure: S. Gaballah: None. B. Horman: None. G. St Armour: None. K. Hoffman: None. H.B. Patisaul: None. H. Stapleton: None. In utero exposure to polybrominated diphenyl ethers (PBDEs) has been linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase out, PBDEs are still measured in newborn cord blood. While evidence suggests that PBDEs can cross the placental barrier, few studies have assessed differences in PBDE or TH accumulation in the maternally and fetally-derived placental tissue layers or studied fetal sex-differences. To address these gaps, we conducted a controlled exposure study in Wistar rats (n=8 per treatment and gestational day (GD)). From GD2, pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose mixture of 10 PBDEs. The low dose represents the 95th percentile of PBDEs measured in U.S. house dust, and the high dose is ∼20X higher. At GD15 and GD20, dams were sacrificed and placental tissues were micro-dissected into maternally and fetally-derived layers. Tissues were analyzed for PBDEs and for T3, rT3, and T4 using mass spectrometry. BDEs 47, 99, 100, and 209 were frequently detected in the fetal and maternal tissues. Higher concentrations of BDEs 99, 100, and 209 were measured in the fetal placenta on GD 15; however, this trend flipped at GD20, with higher maternal concentrations of BDEs 47, 99, and 209. This shift appears to be related to changes in the mass of the maternal and fetal layers during gestation and not to different partioning processes. Only BDE 99 was significantly different between the two layers, in both sexes. At both timepoints, T3 levels were several-fold higher in maternal tissues than fetal, but T3 decreased in maternal tissues by GD20. No sex differences were observed. In general, we observed a significant difference in maternal and fetal T3 levels at GD15 and GD20 in control, low, and high dose-exposed animals. At GD15, there was a significant difference between maternal and fetal female placental T4 levels (p=0.0237) and a suggestive difference in males (p=0.081) in the high dose group, as well as a significant effect of sex between the fetal tissues in the low dose group (p=0.0044). T4 was only detected in the fetal side at GD20, with no significant effects of treatment or sex. These results highlight the rapid developmental changes throughout gestation between the maternal and fetal placenta. Overall, these data highlight that PBDE accumulation in Wistar rats changes across gestation, causing disruption of TH levels in maternal and fetal tissues, and that sex-specific differences may be contributing to differential accumulation patterns in male and female-associated placentas. Coupled with rapid morphological changes in the fetal and maternal layers during placental growth, in utero PBDE exposure may result in adverse impacts on placental TH regulation and fetal health. Presentation: Thursday, June 15, 2023