Prenatal Phenol Exposure and Expression of Imprinted Genes in Human Placenta

Abstract

ISEE-0086 Background and Objective: Many phenols are hormonally active and are thought to impact human development. Alteration of imprinted gene expression in placenta may be one underlying mechanism. Methods: We measured 8 phenol metabolites in urine and amniotic fluid from 11 women enrolled in a prospective pregnancy cohort for assessing toxicant exposures in women undergoing amniocentesis. We examined the relation between analyte concentrations in urine adjusted for specific gravity and expression of imprinted genes in placentas. Results: 2,5-Dichlorophenol (25-DCP), methyl paraben (MPB), and ethyl paraben (EPB) were detected in all urine samples while triclosan was detected in 10 of 11 samples. Neither 25-DCP nor EPB were detected in amniotic fluid. Phenol metabolites most frequently detected in amniotic fluid were MPB and benzophenone-3 (BP-3). We observed no correlation between amniotic fluid and urinary concentrations of MPB; however, amniotic fluid and urine concentrations of BP-3 were highly correlated (R-square >0.7). Bisphenol-A (BPA) was detected in 3 of 3 urine samples from women who delivered large for gestational age babies as compared to 1 of 8 samples for average sized babies. The most biologically active analytes appear to be BP-3, BPA, and 25-DCP; associations between biomarker level and gene expression levels were observed for 20, 17, and 14 imprinted genes, respectively. The gene most sensitive to phenol exposure appears to be HYMA1, with higher levels of 5 biomarkers. BMPR2, WT1, MKRN3, and CTNNA3 were each associated with higher levels of 4 biomarkers. Conclusion: Biomarkers of phenol exposure were detectable in prenatal urine and amniotic fluid. Continued exploration of the effect of phenols on human development is warranted given the high rate of detection in this vulnerable population combined with the observed potential for dysregulating placental gene expression.