Body Burdens of Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls and Their Relations to Estrogen Metabolism in Pregnant Women

Polychlorinated dibenzo-p-dioxins (PCDDs, dioxins), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are environmental endocrine disruptors that have half-lives of 7-10 years in the human body and have toxicities that probably include carcinogenesis. A high ratio of 4-hydroxyl estradiol ($4-OH-E_2$) to 2-hydroxyl estradiol ($2-OH-E_2$) has been suggested as a potential biomarker for estrogen-dependent neoplasms. In this cohort study of maternal-fetal pairs, we examined the relationship of PCDD/PCDF and PCB exposure to levels of estrogen metabolites in the sera of 50 pregnant women 25-34 years of age from central Taiwan. Maternal blood was collected during the third trimester, and the placenta was collected at delivery. We measured 17 dioxin congeners, 12 dioxin-like PCBs, and 6 indicator PCBs in placenta using gas chromatography coupled with high-resolution mass spectrometry. Estrogen metabolites in maternal serum were analyzed by liquid chromatography tandem mass spectrometry. The ratio of $4-OH-E_2:2-OH-E_2$ decreased with increasing exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin ($\beta = -0.124$, p = 0.004 by the general linear regression model, R = 0.4). Meanwhile, serum levels of $4-OH-E_2$ increased with increasing concentrations of high-chlorinated PCDFs (i.e., 1,2,3,4,6,7,8-hepta-CDF: $\beta = 0.454$, p = 0.03, R = 0.30). Altered estrogen catabolism might be associated with body burdens of PCDDs/PCDFs. Our study suggests that exposure to PCDDs/PCDFs significantly affects estrogen metabolism. Therefore, PCDD/PCDF exposure must be considered when using the $OH-E_2$ ratio as a breast cancer marker.