Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

Abstract

People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites). Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

Associations of urinary phthalate metabolites and lipid peroxidation with sperm mitochondrial DNA copy number and deletions

“…Consistent with others (Ferguson et al, 2014, 2015; Holland et al, 2016) and our previous study among a subset of male and female members of the SEEDS cohort (n = 50 couples), we observed urinary phthalate metabolite concentrations to be positively associated with biomarkers of oxidative stress among adults of reproductive age (Wu et al, 2017c). Therefore, we hypothesized that sperm mtDNAcn and mtDNAdel would be positively associated with urinary phthalate metabolite and isoprostane concentrations.…”

“…Oxidative stress measures have been associated with diminished semen quality, including sperm motility, concentration, and morphology (Agarwal et al, 2014). Isoprostanes, formed by the presence of free radicals and commonly used markers of lipid peroxidation in vivo (Kadiiska et al, 2005; Roberts and Morrow, 2002), have been reported to be strongly associated with urinary phthalate metabolite concentrations among pregnant women (Ferguson et al, 2014, 2015; Holland et al, 2016) as well as in our previous study among couples seeking fertility treatment (Wu et al, 2017c). Similarly, a study of couples planning pregnancy reported that select urinary phthalate metabolite concentrations in both males and females were correlated with urinary 8-Oxo-2′-deoxyguanosine concentrations, a biomarker of oxidative stress via DNA oxidation (Guo et al, 2014).…”

Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood

“…Phthalate metabolite concentrations in CHAMACOS mothers [Holland et al, ; Huen et al, ] were comparable to those of pregnant women from the National Health and Nutrition Examination Survey [Woodruff et al, ]. The distribution of creatinine‐adjusted urinary phthalate metabolite concentrations measured in the subset of subjects included in the current study are shown in Table , and did not differ from the total cohort [Holland et al, ]. MEP was the metabolite with the highest concentrations while MCNP had the lowest concentrations among 11 phthalates metabolites that were assessed.…”

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

“…Oxidative stress is implicated in adverse reproductive conditions including sperm DNA damage (Gavriliouk and Aitken, 2015), endometriosis (Mier-Cabrera et al, 2011; Sharma et al, 2010), and polycystic ovary syndrome (Palacio et al, 2006). Additionally, recent evidence suggests strong positive associations between urinary phthalate metabolite concentrations and biomarkers of oxidative stress among pregnant women (Ferguson et al, 2014; Ferguson et al, 2015; Holland et al, 2016), couples who were planning pregnancy (Guo et al, 2014), and the general US population (Ferguson et al, 2012). Most recently, oxidative stress was shown to partially mediate the association of phthalate exposure on preterm birth in Puerto Rico (Ferguson et al, 2016).…”