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Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort
BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382502/ https://www.ncbi.nlm.nih.gov/pubmed/28381288 http://dx.doi.org/10.1186/s12940-017-0241-5 |
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author | Adibi, Jennifer J. Buckley, Jessie P. Lee, Myoung Keun Williams, Paige L. Just, Allan C. Zhao, Yaqi Bhat, Hari K. Whyatt, Robin M. |
author_facet | Adibi, Jennifer J. Buckley, Jessie P. Lee, Myoung Keun Williams, Paige L. Just, Allan C. Zhao, Yaqi Bhat, Hari K. Whyatt, Robin M. |
author_sort | Adibi, Jennifer J. |
collection | PubMed |
description | BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of log(e) mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 log(e) units lower at the 3(rd) vs. 1(st) quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): −3.5, −0.5) in male placentas, but 0.6 log(e) units higher (95% CI: −0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (−1.1 log(e) units at highest vs. lowest quartile, 95% CI: −2.0, −0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: −2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-017-0241-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5382502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53825022017-04-10 Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort Adibi, Jennifer J. Buckley, Jessie P. Lee, Myoung Keun Williams, Paige L. Just, Allan C. Zhao, Yaqi Bhat, Hari K. Whyatt, Robin M. Environ Health Research BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of log(e) mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 log(e) units lower at the 3(rd) vs. 1(st) quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): −3.5, −0.5) in male placentas, but 0.6 log(e) units higher (95% CI: −0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (−1.1 log(e) units at highest vs. lowest quartile, 95% CI: −2.0, −0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: −2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-017-0241-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-04-05 /pmc/articles/PMC5382502/ /pubmed/28381288 http://dx.doi.org/10.1186/s12940-017-0241-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Adibi, Jennifer J. Buckley, Jessie P. Lee, Myoung Keun Williams, Paige L. Just, Allan C. Zhao, Yaqi Bhat, Hari K. Whyatt, Robin M. Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title | Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title_full | Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title_fullStr | Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title_full_unstemmed | Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title_short | Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort |
title_sort | maternal urinary phthalates and sex-specific placental mrna levels in an urban birth cohort |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382502/ https://www.ncbi.nlm.nih.gov/pubmed/28381288 http://dx.doi.org/10.1186/s12940-017-0241-5 |
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