Urinary phthalate metabolites are associated with biomarkers of DNA damage and lipid peroxidation in pregnant women – Tainan Birth Cohort Study (TBCS)

Phthalate exposure and oxidative stress have been linked to adverse reproductive outcomes in experimental studies, whereas no clear line has been drawn for human, especially in pregnant women. This study explored relationships between urinary phthalate metabolites and biomarkers of lipid peroxidatio...

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Published in:Environmental research 2020-09, Vol.188, p.109863, Article 109863
Main Authors: Waits, Alexander, Chen, Hsin-Chang, Kuo, Pao-Lin, Wang, Chih-Wen, Huang, Han-Bin, Chang, Wei-Hsiang, Shih, Shu-Fang, Huang, Po-Chin
Format: Article
Language:English
Subjects:
DNA damage
Lipid peroxidation
Nitrosative stress
Oxidative stress
Phthalate
Pregnancy
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Summary:Phthalate exposure and oxidative stress have been linked to adverse reproductive outcomes in experimental studies, whereas no clear line has been drawn for human, especially in pregnant women. This study explored relationships between urinary phthalate metabolites and biomarkers of lipid peroxidation and oxidative and nitrosative DNA damage. Measurements from 97 Taiwanese pregnant women were taken at three different times during second and third 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 visit and linear mixed-model regressions were fitted to estimate percent changes in oxidative/nitrosative stress biomarkers resulting from inter-tertile increase of phthalate metabolite level and the cumulative concentrations of di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate. 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 visit and in repeated measurements analysis, respectively. Of the biomarkers related to DNA damage, 8-OHdG (25.4% inter-tertile increase for mono-iso-butyl phthalate) was more sensitive to phthalate exposure than 8-NO2Gua. Among the biomarkers of lipid peroxidation, HNE-MA (61.2% inter-tertile increase for sum of DEHP metabolites) was more sensitive than 8-isoPF2α and MDA. Our findings support the hypothesis that pregnant phthalate exposure increases the oxidative stress biomarkers of DNA damage and lipid peroxidation. Future research may elucidate the mediating roles of oxidative/nitrosative stress biomarkers in the link between phthalate exposure and adverse reproductive outcomes. •Pregnant phthalate exposure was associated with oxidative stress biomarkers of DNA damage/lipid peroxidation.•Pregnant DnBP exposure was positively associated with 25.4% increase of 8-OHdG.•Pregnant sum DEHP was positively associated with 61.2% increase of HNE-MA.•Enhanced susceptibility to phthalate exposure in the third trimester was observed.
ISSN:0013-9351
1096-0953
DOI:10.1016/j.envres.2020.109863