Urinary Phthalate Metabolite Associations with Biomarkers of Inflammation and Oxidative Stress Across Pregnancy in Puerto Rico

Abstract

Phthalate exposure during pregnancy has been linked to adverse birth outcomes such as preterm birth, and inflammation and oxidative stress may mediate these relationships. In a prospective cohort study of pregnant women recruited early in gestation in Northern Puerto Rico, we investigated the associations between urinary phthalate metabolites and biomarkers of inflammation, including C-reactive protein, IL-1β, IL-6, IL-10, and TNF-α, and oxidative stress, including 8-hydroxydeoxyguanosine (OHdG) and 8-isoprostane. Inflammation biomarkers were measured in plasma twice during pregnancy (N = 215 measurements, N = 120 subjects), and oxidative stress biomarkers in urine were measured three times (N = 148 measurements, N = 54 subjects) per woman. In adjusted linear mixed models, metabolites of di-2-ethylhexyl phthalate (DEHP) were associated with increased IL-6 and IL-10 but relationships were generally not statistically significant. All phthalates were associated with increases in oxidative stress markers. Relationships with OHdG were significant for DEHP metabolites as well as mono-n-butyl phthalate (MBP) and monoiso-butyl phthalate (MiBP). For 8-isoprostane, associations with nearly all phthalates were statistically significant and the largest effect estimates were observed for MBP and MiBP (49–50% increase in 8-isoprostane with an interquartile range increase in metabolite concentration). These relationships suggest a possible mechanism for phthalate action that may be relevant to a number of adverse health outcomes.

Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico

“…Urinary BPA concentrations were weakly or moderately correlated with all phthalate metabolites, with Spearman correlations ranging from 0.17 with both MCNP and MCOP to 0.36 with MiBP. Distributions of and correlations between markers for oxidative stress and inflammation in this study population have been presented elsewhere (Ferguson et al, 2014a). Briefly, the oxidative stress markers isoprostane and OHdG were detected in all urine samples analyzed and were moderately correlated with one another (r = 0.43, p<0.01).…”

“…We calculated geometric means (GM) and standard deviations (GSD), as well as selected percentiles to describe distributions of SG-standardized urinary phenol and paraben concentrations. Distributions of oxidative stress and inflammation biomarkers, as well as correlations between these biomarkers, have been previously described (Ferguson et al, 2014a). …”

“…We recently reported positive associations between urinary phthalate metabolites and markers of oxidative stress in the PROTECT cohort (Ferguson et al, 2014a). Accordingly, we examined Spearman correlations between urinary phthalate metabolites, phenols, and parabens within this study population.…”

Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice

“…It was reported recently that phthalate exposure is associated with increased inflammation and oxidative stress and phthalates activate macrophages in different tissues (Murphy et al, 2014; Campioli et al, 2014; Ferguson et al, 2014). Therefore, using immune-deficient recipient mice may have underestimated the effects of phthalates.…”

Identification and Quantification of Phthalate Pollution in Holothuria atra, a Sea Cucumber from the Persian Gulf (Iran)

“…These phthalates effect the endocrine systems, such as sex hormones and thyroids (4). Previous studies also indicate that phthalates could exhibit inflammation, early puberty in girls, oxidative stress, asthma, and allergic reactions (5)(6)(7). Furthermore, induction of toxicity in the liver, lungs, kidneys and testis has been reported for these compounds (3).…”