Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation

Julia R Varshavsky,Saunak Sen,Julie Frankenfield,Sirirak Buarpung,Susan J Fisher,Joshua F Robinson,June-Soo Park,Elaine Kwan,Stephanie L Gaw,Yan Zhou,Sabrina Crispo Smith,Rayyan Aburajab,Kenisha A Puckett,Tracey J Woodruff

doi:10.1186/s12940-020-00617-7

Abstract

BackgroundPolybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function.MethodsTo evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion—integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)–and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues–leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall’s tau correlation and linear regression methods.ResultsPBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive).ConclusionsWe found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

Highlights

Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes
This indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stagespecific antigens
Motivated by our in vitro exposure data showing that BDE-47 inhibits CTB migration and invasion, we further investigated whether PBDE exposures in vivo were associated with reduced immunoreactivity of molecules that are typically upregulated during these processes

Summary

Introduction

Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. We lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function. Pregnancy complications, such as preterm birth, gestational diabetes, fetal growth restriction, hypertension, and preeclampsia, are significantly linked with adverse maternal and fetal health outcomes [1], and environmental exposures are important risk factors [2,3,4]. Vascular CTB remodeling of uterine arteries redirects blood flow to the placenta, maximizing nutrient uptake for embryonic/fetal growth and development over the course of gestation [7]. Placental development (placentation) is especially critical during mid-gestation, an important time of fetal organogenesis and extreme changes to maternal physiology [4]

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Conclusion