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Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy.

ABSTRACT: Maternal urinary biomarkers are often used to assess fetal exposure to phenols and their precursors. Their effectiveness as a measure of exposure in epidemiological studies depends on their variability during pregnancy and their ability to accurately predict fetal exposure.We assessed the relationship between urinary and amniotic fluid concentrations of nine environmental phenols, and the reproducibility of urinary concentrations, among pregnant women.Seventy-one women referred for amniocentesis were included. Maternal urine was collected at the time of the amniocentesis appointment and on two subsequent occasions. Urine and amniotic fluid were analyzed for 2,4- and 2,5-dichlorophenols, bisphenol A, benzophenone-3, triclosan, and methyl-, ethyl-, propyl-, and butylparabens using online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry.Only benzophenone-3 and propylparaben were detectable in more than half of the amniotic fluid samples; for these phenols, concentrations in amniotic fluid and maternal urine collected on the same day were positively correlated (? = 0.53 and 0.32, respectively). Other phenols were detected infrequently in amniotic fluid (e.g., bisphenol A was detected in only two samples). The intraclass correlation coefficients (ICCs) of urinary concentrations in samples from individual women ranged from 0.48 and 0.62 for all phenols except bisphenol A (ICC = 0.11).Amniotic fluid detection frequencies for most phenols were low. The reproducibility of urine measures was poor for bisphenol A, but good for the other phenols. Although a single sample may provide a reasonable estimate of exposure for some phenols, collecting multiple urine samples during pregnancy is an option to reduce exposure measurement error in studies regarding the effects of phenol prenatal exposure on health.

SUBMITTER: Philippat C

PROVIDER: S-EPMC3801458 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy.

Philippat Claire C Wolff Mary S MS Calafat Antonia M AM Ye Xiaoyun X Bausell Rebecca R Meadows Molly M Stone Joanne J Slama Rémy R Engel Stephanie M SM

Environmental health perspectives 20130813 10

<h4>Background</h4>Maternal urinary biomarkers are often used to assess fetal exposure to phenols and their precursors. Their effectiveness as a measure of exposure in epidemiological studies depends on their variability during pregnancy and their ability to accurately predict fetal exposure.<h4>Objectives</h4>We assessed the relationship between urinary and amniotic fluid concentrations of nine environmental phenols, and the reproducibility of urinary concentrations, among pregnant women.<h4>Me ...[more]

PMID: 23942273

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Project description:BACKGROUND:Phenols and phthalates are potential endocrine disrupting chemicals (EDCs) that are associated with adverse health outcomes. These EDCs dysregulate a number of biomolecules and pathways, including microRNAs. MicroRNAs can be carried in transport systems called extracellular vesicles (EVs) that are present in most biofluids. EVs in the follicular fluid, which fills the ovarian follicle and influences oocyte developmental competency, carry microRNAs (EV-miRNAs) that have been associated with In Vitro Fertilization (IVF) outcomes. However, it remains unclear whether EDCs affect EV-miRNAs in follicular fluid. OBJECTIVES:This study sought to determine whether urinary concentrations of phenols and phthalates biomarkers are associated with EV-miRNAs expression in follicular fluid collected from women undergoing IVF treatment. METHODS:This cross-sectional study included 130 women recruited between January 2014 and August 2016 in a tertiary university-affiliated hospital. Participants provided urine samples during ovarian stimulation and on the day of oocyte retrieval. We assessed urinary concentrations of five phenols, eight phthalate metabolites, and one phthalate alternative metabolite. EV-miRNAs were isolated from follicular fluid and their expression profiles were measured using the TaqMan Open Array® Human microRNA panel. We fitted multivariable linear regression models and principal component analysis to examine associations between individual and molar sums of exposure biomarkers and EV-miRNAs. RESULTS:Of 754 miRNAs tested, we detected 133 EV-miRNAs in the microRNA array which expressed in at least 50% of the follicular fluid samples. After adjusting for multiple testing, we identified eight EV-miRNAs associated with individual phenols and phthalate metabolites, as well as molar ?DEHP that met a q?<?0.10 false-discovery rate (FDR) threshold. Hsa-miR-125b, hsa-miR-106b, hsa-miR-374a, and hsa-miR15b was associated with mono(2-ethylhexyl) phthalate concentrations, hsa-let-7c with concentrations mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and the sum of metabolites of di(2-ethylhexyl) phthalate, hsa-miR-24 with mono-n-butyl phthalate concentrations, hsa-miR-19a with cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH), and hsa-miR-375 with ethyl paraben concentrations. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, gene targets and pathways of these EV-miRNAs were predicted in silico and 17 KEGG FDR-significant pathways related to follicular development and oocyte competence were identified. CONCLUSIONS:Our results show that urinary concentrations of select phenol and phthalate metabolites are correlated with altered EV-miRNAs expression in follicular fluid. These findings may provide insight regarding the molecular mechanisms underlying adverse effects of phenol and phthalate exposure on female fertility.

Project description:BackgroundEnvironmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI).MethodsParticipants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996-1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models.ResultsThe highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI < 25.0 kg/m2 than among women with BMI ≥ 25.0 kg/m2; however, associations for mortality were more pronounced among women with BMI ≥ 25 kg/m2 than among women with BMI < 25 kg/m2.ConclusionsSelect parabens may have differential associations with risk of developing breast cancer and mortality following breast cancer.

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Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy.

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Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy.

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