Abstract
INTRODUCTION: Placental development, involving rapid vascularization, is regulated by concentration gradients of numerous growth factors and hormones. Placental growth factor (PlGF) promotes vasculogenesis and angiogenesis in the placenta, while soluble fms-like tyrosine kinase-1 (sFlt-1) inhibits these processes. An elevated ratio of sFlt-1/PlGF in maternal serum is predictive of preeclampsia. Exposure to two classes of ubiquitous endocrine-disrupting chemicals, bisphenols and phthalates, has also been previously linked to preeclampsia development. METHODS: We investigated the relation of urinary concentrations of bisphenols and phthalate metabolites, measured up to three times during pregnancy, with serum concentrations of sFlt-1, PlGF, and their ratio in the New York University Children's Health and Environment Study. Linear mixed models were used to analyze up to three measurements of PlGF and sFlt-1 adjusted for gestational age at the time of serum collection. RESULTS: We found that higher molar sum concentration of bisphenol A and bisphenol S was associated with lower sFlt-1 (-0.12, 95 % CI: -0.22, -0.03), higher PlGF (0.08, 95 % CI: -0.01, 0.18), and lower sFlt-1/PlGF ratio (-0.12, 95 % CI: -0.21, -0.02). Phthalic acid and metabolites of anti-androgenic and low molecular weight phthalates were similarly associated with higher PlGF and lower sFlt-1/PlGF, but only after 20 weeks of gestation. DISCUSSION: The unexpected relationship between prenatal bisphenol and phthalate exposure and lower sFlt-1/PlGF warrants further investigation. Our results suggest that the effect of these endocrine-disrupting chemicals on placental health may be more complicated than what is currently understood through these angiogenic biomarkers.