Dataset Information

Urinary glycol ether metabolites in women and time to pregnancy: the PELAGIE cohort.

ABSTRACT:

Background

Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function.

Objective

We examined the relation between women's exposure to glycol ethers and time to pregnancy.

Methods

We used chromatography coupled to mass spectrometry to measure eight glycol ether metabolites in urine samples from randomly selected women in the PELAGIE mother-child cohort who had samples collected before 19 weeks of gestation. Using time to pregnancy information collected at the beginning of the pregnancy (women were asked how many months it took for them to conceive), we estimated associations between metabolite levels and time to pregnancy in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders.

Results

We detected glycol ether metabolites in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy [fecundability OR = 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR = 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (? 1.38 mg/L) vs. first-quartile concentration (< 0.14 mg/L)]. This association remained stable after multiple sensitivity analyses.

Conclusion

Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but they may also be surrogates for potential coexposures to compounds frequently present in cosmetics.

SUBMITTER: Garlantezec R

PROVIDER: S-EPMC3801453 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Urinary glycol ether metabolites in women and time to pregnancy: the PELAGIE cohort.

Garlantézec Ronan R Warembourg Charline C Monfort Christine C Labat Laurence L Pulkkinen Juha J Bonvallot Nathalie N Multigner Luc L Chevrier Cécile C Cordier Sylvaine S

Environmental health perspectives 20130709 10

<h4>Background</h4>Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function.<h4>Objective</h4>We examined the relation between women's exposure to glycol ethers and time to pregnancy.<h4>Methods</h4>We used chromatography coupled to mass spectrometry to measure eight glycol ether metabolites in urine samples from randomly selected women in the PELAGIE mother-child cohort who had samples collected ...[more]

PMID: 23838187

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Project description:BackgroundGlycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children.ObjectivesWe investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother-child cohort.MethodsFive GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child's stimulation at home.ResultsGE metabolites were detected in 90-100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [β (third vs. first tertile) = -6.53; 95% CI: -11.44, -1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [β (third vs. first tertile) = -0.11; 95% CI: -0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores.ConclusionsPrenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children.

Project description:In recent decades, the detrimental effects of environmental contaminants on human health have become a serious public concern. Organophosphate (OP) pesticides are widely used in agriculture, and the negative impacts of OP and its metabolites on human health have been demonstrated. We hypothesized that exposure to OPs during pregnancy could impose damaging effects on the fetus by affecting various processes. We analyzed sex-specific epigenetic responses in the placenta samples obtained from the mother-child PELAGIE cohort. We assayed the telomere length and mitochondrial copy numbers using genomic DNA. We analyzed H3K4me3 by using chromatin immunoprecipitation followed by qPCR (ChIP‒qPCR) and high-throughput sequencing (ChIP-seq). The human study was confirmed with mouse placenta tissue analysis. Our study revealed a higher susceptibility of male placentas to OP exposure. Specifically, we observed telomere length shortening and an increase in γH2AX levels, a DNA damage marker. We detected lower histone H3K9me3 occupancy at telomeres in diethylphosphate (DE)-exposed male placentas than in nonexposed placentas. We found an increase in H3K4me3 occupancy at the promoters of thyroid hormone receptor alpha (THRA), 8-oxoguanine DNA glycosylase (OGG1) and insulin-like growth factor (IGF2) in DE-exposed female placentas. H3K4me3 occupancy at PPARG was increased in both male and female placentas exposed to dimethylphosphate (DM). The genome-wide sequencing of selected samples revealed sex-specific differences induced by DE exposure. Specifically, we found alterations in H3K4me3 in genes related to the immune system in female placenta samples. In DE-exposed male placentas, a decrease in H3K4me3 occupancy at development-related, collagen and angiogenesis-related genes was observed. Finally, we observed a high number of NANOG and PRDM6 binding sites in regions with altered histone occupancy, suggesting that the effects were possibly mediated via these factors. Our data suggest that in utero exposure to organophosphate metabolites affects normal placental development and could potentially impact late childhood.

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Dataset Information

Urinary glycol ether metabolites in women and time to pregnancy: the PELAGIE cohort.

Background

Objective

Methods

Results

Conclusion

Publications

Urinary glycol ether metabolites in women and time to pregnancy: the PELAGIE cohort.

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