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DOI | 10.1289/EHP8973 |
A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape | |
Alison G. Paquette; James MacDonald; Samantha Lapehn; Theo Bammler; Laken Kruger; Drew B. Day; Nathan D. Price; Christine Loftus; Kurunthachalam Kannan; Carmen Marsit; W. Alex Mason; Nicole R. Bush; Kaja Z. LeWinn; Daniel A. Enquobahrie; Bhagwat Prasad; Catherine J. Karr; Sheela Sathyanarayana | |
2021-09-03 | |
发表期刊 | Environmental Health Perspectives |
出版年 | 2021 |
英文摘要 | AbstractBackground:Phthalates are commonly used endocrine-disrupting chemicals that are ubiquitous in the general population. Prenatal phthalate exposure may alter placental physiology and fetal development, leading to adverse perinatal and childhood health outcomes. Objective:We examined associations between prenatal phthalate exposure in the second and third trimesters and the placental transcriptome at birth, including genes and long noncoding RNAs (lncRNAs), to gain insight into potential mechanisms of action during fetal development. Methods:The ECHO PATHWAYs consortium quantified 21 urinary phthalate metabolites from 760 women enrolled in the CANDLE study (Shelby County, TN) using high-performance liquid chromatography–tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate separate associations between maternal urinary phthalate metabolite concentration during the second and third trimester and placental gene expression at birth, adjusted for confounding variables. Genes were considered differentially expressed at a Benjamini-Hochberg false discovery rate (FDR) . Associations between phthalate metabolites and biological pathways were identified using self-contained gene set testing and considered significantly altered with an FDR-adjusted . Results:We observed significant associations between second-trimester phthalate metabolites mono (carboxyisooctyl) phthalate (MCIOP), mono-2-ethyl-5-carboxypentyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate and 18 genes in total, including four lncRNAs. Specifically, placental expression of NEAT1 was associated with multiple phthalate metabolites. Third-trimester MCIOP and mono-isobutyl phthalate concentrations were significantly associated with placental expression of 18 genes and two genes, respectively. Expression of genes within 27 biological pathways was associated with mono-methyl phthalate, MCIOP, and monoethyl phthalate concentrations. Discussion:To our knowledge, this is the first genome-wide assessment of the relationship between the placental transcriptome at birth and prenatal phthalate exposure in a large and diverse birth cohort. We identified numerous genes and lncRNAs associated with prenatal phthalate exposure. These associations mirror findings from other epidemiological and in vitro analyses and may provide insight into biological pathways affected in utero by phthalate exposure. https://doi.org/10.1289/EHP8973 |
领域 | 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/337500 |
专题 | 资源环境科学 |
推荐引用方式 GB/T 7714 | Alison G. Paquette,James MacDonald,Samantha Lapehn,et al. A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape[J]. Environmental Health Perspectives,2021. |
APA | Alison G. Paquette.,James MacDonald.,Samantha Lapehn.,Theo Bammler.,Laken Kruger.,...&Sheela Sathyanarayana.(2021).A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape.Environmental Health Perspectives. |
MLA | Alison G. Paquette,et al."A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape".Environmental Health Perspectives (2021). |
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