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Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico.

ABSTRACT: Context:Phthalates are endocrine-disrupting chemicals that may be associated with adverse birth outcomes. Dysregulation of maternal endocrine homeostasis could be a possible biological pathway between phthalates and birth outcomes. Objective:Examine associations between 19 maternal urinary phthalate or phthalate replacement metabolites and 9 serum hormones measured over two time points during pregnancy. Design:Longitudinal study conducted in the PROTECT pregnancy cohort. Setting:Puerto Rico. Patients:Six hundred seventy-seven women in the first trimester of pregnancy. Main Outcome Measures Serum:CRH, estriol, SHBG, progesterone, TSH, total T3, free T4, total T4, and testosterone. Results:T3 was significantly associated with most metabolites. CRH was inversely associated with mono carboxyisononyl phthalate [MCNP; percent change (%?), -4.08; 95% CI, -7.24, -0.804], mono-3-carboxypropyl phthalate (MCPP; %?, -5.25; 95% CI, -8.26, -2.14), mono-2-ethyl-5-carboxypentyl phthalate (MECPP; %?, -18.4; 95% CI, -30.4, -4.37), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; %?, -13.4; 95% CI, -22.7, -2.92), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP; %?, -12.7; 95% CI, -22.2, -2.20). Positive associations were found between numerous phthalate metabolites and free T4, T4, and the T3/T4 ratio. Testosterone was positively associated with mono hydroxybutyl phthalate (MHBP; %?, 4.71; 95% CI, 0.27, 9.35) and inversely associated with monoethyl phthalate (MEP; %?, -14.5; 95% CI, -24.3, -3.42), and relationships with MCNP and mono carboxyisooctyl phthalate (MCOP) were significantly modified by study visit. Finally, an inverse association was found between mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP), a terephthalate metabolite, and progesterone at visit 3 only (%?, -13.1; 95% CI, -22.3, -2.75). Conclusions:These results indicate that exposure to phthalates may differentially impact the maternal endocrine system at different points during pregnancy, and that exposures to phthalate replacement chemicals may be particularly important to consider in future human health studies.

SUBMITTER: Cathey AL

PROVIDER: S-EPMC6510018 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico.

Cathey Amber L AL Watkins Deborah D Rosario Zaira Y ZY Vélez Carmen C Alshawabkeh Akram N AN Cordero José F JF Meeker John D JD

Journal of the Endocrine Society 20190411 6

<h4>Context</h4>Phthalates are endocrine-disrupting chemicals that may be associated with adverse birth outcomes. Dysregulation of maternal endocrine homeostasis could be a possible biological pathway between phthalates and birth outcomes.<h4>Objective</h4>Examine associations between 19 maternal urinary phthalate or phthalate replacement metabolites and 9 serum hormones measured over two time points during pregnancy.<h4>Design</h4>Longitudinal study conducted in the PROTECT pregnancy cohort.<h4 ...[more]

PMID: 31093596

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Project description:BackgroundPhthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.ObjectiveTo explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.MethodsWe measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.ResultsAfter controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains.SignificanceCharacterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes.ImpactThis study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.

Project description:BackgroundMetal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes.MethodsPregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations.ResultsArsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4-39.6) and decreased levels in testosterone (%Δ: -16.3, 95%CI: -26.2--5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3-4.2), E3 (%Δ range: 3.9-8.7) and progesterone (%Δ range: 4.1-6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ -13.3, 95%CI: -18.7--7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01).ConclusionOur analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.

Project description:Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1?, IL-6, IL-10, and tumor necrosis factor-? (TNF-?)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed.

Dataset Information

Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico.

Publications

Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico.

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