Association between Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in Pregnant Women - Tainan Birth Cohort Study (TBCS)

Abstract

BACKGROUND AND AIM: Oxidative stress biomarkers were suggested to be intermediates link between phthalate exposure and adverse health outcomes in pregnant women. This study explored the relationship between urinary phthalate metabolites and biomarkers indicative of lipid peroxidation and oxidative and nitrosative DNA damage. METHODS: Measurements from 97 Taiwanese women were taken across three trimesters. Five oxidative/nitrosative stress biomarkers - 8-hydroxy-2′deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA), and 11 phthalate metabolites were measured in urine samples. Linear regressions in each trimester and a linear mixed-model regression were fitted to estimate percent changes in oxidative/nitrosative stress biomarkers resulting from any inter-tertile increase of phthalate metabolite level and the cumulative concentration of di (2-ethylhexyl) phthalate and dibutyl phthalate. RESULTS:The highest urine concentrations of phthalate metabolites and the greatest number of significant positive associations between phthalate metabolites and oxidative/nitrosative stress biomarkers were observed in the third trimester and through repeated measurements analysis, respectively. Of the biomarkers related to DNA damage, 8-OHdG (25.4% increasing for monoiso-butyl phthalate tertile increased) was more sensitive to phthalate exposure than 8-NO2Gua. Among the biomarkers of lipid peroxidation, HNE-MA (61.2% increasing for sum DEHP tertile increased) was more sensitive than 8-isoPF2α and MDA. CONCLUSIONS:Our results suggest an enhanced susceptibility to phthalate exposure in the third trimester. Future research is necessary to evaluate the mediating role of oxidative/nitrosative stress biomarkers in the link between phthalate exposure and adverse reproductive outcomes. KEYWORDS: Phthalate, Oxidative stress, Nitrosative stress, DNA damage, Lipid peroxidation, Pregnancy