Maternal-Fetal Polybrominated Diphenyl Ether (PBDE) Levels and Biomarkers of Placental Development and Disease during Mid-gestation

Abstract

While the mechanisms and periods of sensitivity remain undefined, in utero exposures to polybrominated diphenyl ethers (PBDEs) may be linked with placenta-mediated pregnancy complications. To define the relationship between PBDE exposure and placental development, we performed: 1) an evaluation of PBDE exposures in matched samples of maternal serum, placenta, and the fetal liver collected from healthy pregnant women undergoing elective terminations during mid-gestation (n=180; 2014-16); and 2) a semi-qualitative characterization of biomarkers of placental development in relation to placental PBDE levels (n=62). Study protocols were approved by the University of California, San Francisco institutional review board; written and verbal consent were obtained from each study participant. We used censored Kendall’s tau correlation and maximum likelihood regression to compare PBDE levels between maternal-fetal tissues and examine their associations with biomarkers of placental development and disease. We profiled placental cytotrophoblast (CTB) expression of integrin alpha 1 (ITGA1) and vascular endothelial-cadherin (CDH5) and metalloproteinase 1 (MMP1). In addition, we evaluated morphological features: leukocyte recruitment (basal plate), fibrinoid deposition (villous, basal plate), and CTB endovascular invasion. PBDEs were detected in all biomatrices. Prior to lipid adjustment, wet-weight PBDE levels were highest in the fetal liver compared to other compartments (p<0.001). In contrast, after lipid adjustment, PBDE levels were higher in maternal serum compared to the fetal liver and placenta (p<0.001). We observed associations between placental PBDE levels and endovascular CTB immunoreactivity of ITGA1 (inverse) and interstitial CTB immunoreactivity of CDH5 (positive), suggesting these markers of CTB invasion and development may be sensitive placental biomarkers of PBDE exposure. Our work suggests that PBDEs are widely detected and differentially distributed in maternal-fetal compartments. Furthermore, we propose specific biomarkers of placental development as potential barometers of PBDE exposure during mid-gestation. This paradigm could be extended to other environmental chemicals and placental biomarkers.