Cargando…
Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants originating from petrogenic and pyrogenic sources. PAH compounds can cross the placenta, and prenatal PAH exposure is linked to adverse infant and childhood health outcomes. OBJECTIVE: In this first human transcriptomic as...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10211546/ https://www.ncbi.nlm.nih.gov/pubmed/36689866 http://dx.doi.org/10.1016/j.envint.2023.107763 |
_version_ | 1785047291965472768 |
---|---|
author | Paquette, Alison G. Lapehn, Samantha Freije, Sophie MacDonald, James Bammler, Theo Day, Drew B. Loftus, Christine T. Kannan, Kurunthachalam Mason, W. Alex Bush, Nicole R. LeWinn, Kaja Z Enquobahrie, Daniel A. Marsit, Carmen Sathyanarayana, Sheela |
author_facet | Paquette, Alison G. Lapehn, Samantha Freije, Sophie MacDonald, James Bammler, Theo Day, Drew B. Loftus, Christine T. Kannan, Kurunthachalam Mason, W. Alex Bush, Nicole R. LeWinn, Kaja Z Enquobahrie, Daniel A. Marsit, Carmen Sathyanarayana, Sheela |
author_sort | Paquette, Alison G. |
collection | PubMed |
description | BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants originating from petrogenic and pyrogenic sources. PAH compounds can cross the placenta, and prenatal PAH exposure is linked to adverse infant and childhood health outcomes. OBJECTIVE: In this first human transcriptomic assessment of PAHs in the placenta, we examined associations between prenatal PAH exposure and placental gene expression to gain insight into mechanisms by which PAHs may disrupt placental function. METHODS: The ECHO PATHWAYS Consortium quantified prenatal PAH exposure and the placental transcriptome from 629 pregnant participants enrolled in the CANDLE study. Concentrations of 12 monohydroxy-PAH (OH-PAH) metabolites were measured in mid-pregnancy urine using high performance liquid chromatography tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate covariate-adjusted associations between maternal urinary OH-PAHs and placental gene expression. We performed sex-stratified analyses to evaluate whether associations varied by fetal sex. Selected PAH/gene expression analyses were validated by treating HTR-8/SVneo cells with phenanthrene, and quantifying expression via qPCR. RESULTS: Urinary concentrations of 6 OH-PAHs were associated with placental expression of 8 genes. Three biological pathways were associated with 4 OH-PAHs. Placental expression of SGF29 and TRIP13 as well as the vitamin digestion and absorption pathway were positively associated with multiple metabolites. HTR-8/SVneo cells treated with phenanthrene also exhibited 23% increased TRIP13 expression compared to vehicle controls (p = 0.04). Fetal sex may modify the relationship between prenatal OH-PAHs and placental gene expression, as more associations were identified in females than males (45 vs 28 associations). DISCUSSION: Our study highlights novel genes whose placental expression may be disrupted by OH-PAHs. Increased expression of DNA damage repair gene TRIP13 may represent a response to double-stranded DNA breaks. Increased expression of genes involved in vitamin digestion and metabolism may reflect dietary exposures or represent a compensatory mechanism to combat damage related to OH-PAH toxicity. Further work is needed to study the role of these genes in placental function and their links to perinatal outcomes and lifelong health. |
format | Online Article Text |
id | pubmed-10211546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-102115462023-05-25 Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons Paquette, Alison G. Lapehn, Samantha Freije, Sophie MacDonald, James Bammler, Theo Day, Drew B. Loftus, Christine T. Kannan, Kurunthachalam Mason, W. Alex Bush, Nicole R. LeWinn, Kaja Z Enquobahrie, Daniel A. Marsit, Carmen Sathyanarayana, Sheela Environ Int Article BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants originating from petrogenic and pyrogenic sources. PAH compounds can cross the placenta, and prenatal PAH exposure is linked to adverse infant and childhood health outcomes. OBJECTIVE: In this first human transcriptomic assessment of PAHs in the placenta, we examined associations between prenatal PAH exposure and placental gene expression to gain insight into mechanisms by which PAHs may disrupt placental function. METHODS: The ECHO PATHWAYS Consortium quantified prenatal PAH exposure and the placental transcriptome from 629 pregnant participants enrolled in the CANDLE study. Concentrations of 12 monohydroxy-PAH (OH-PAH) metabolites were measured in mid-pregnancy urine using high performance liquid chromatography tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate covariate-adjusted associations between maternal urinary OH-PAHs and placental gene expression. We performed sex-stratified analyses to evaluate whether associations varied by fetal sex. Selected PAH/gene expression analyses were validated by treating HTR-8/SVneo cells with phenanthrene, and quantifying expression via qPCR. RESULTS: Urinary concentrations of 6 OH-PAHs were associated with placental expression of 8 genes. Three biological pathways were associated with 4 OH-PAHs. Placental expression of SGF29 and TRIP13 as well as the vitamin digestion and absorption pathway were positively associated with multiple metabolites. HTR-8/SVneo cells treated with phenanthrene also exhibited 23% increased TRIP13 expression compared to vehicle controls (p = 0.04). Fetal sex may modify the relationship between prenatal OH-PAHs and placental gene expression, as more associations were identified in females than males (45 vs 28 associations). DISCUSSION: Our study highlights novel genes whose placental expression may be disrupted by OH-PAHs. Increased expression of DNA damage repair gene TRIP13 may represent a response to double-stranded DNA breaks. Increased expression of genes involved in vitamin digestion and metabolism may reflect dietary exposures or represent a compensatory mechanism to combat damage related to OH-PAH toxicity. Further work is needed to study the role of these genes in placental function and their links to perinatal outcomes and lifelong health. 2023-02 2023-01-18 /pmc/articles/PMC10211546/ /pubmed/36689866 http://dx.doi.org/10.1016/j.envint.2023.107763 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Paquette, Alison G. Lapehn, Samantha Freije, Sophie MacDonald, James Bammler, Theo Day, Drew B. Loftus, Christine T. Kannan, Kurunthachalam Mason, W. Alex Bush, Nicole R. LeWinn, Kaja Z Enquobahrie, Daniel A. Marsit, Carmen Sathyanarayana, Sheela Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title | Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title_full | Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title_fullStr | Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title_full_unstemmed | Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title_short | Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons |
title_sort | placental transcriptomic signatures of prenatal exposure to hydroxy-polycyclic aromatic hydrocarbons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10211546/ https://www.ncbi.nlm.nih.gov/pubmed/36689866 http://dx.doi.org/10.1016/j.envint.2023.107763 |
work_keys_str_mv | AT paquettealisong placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT lapehnsamantha placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT freijesophie placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT macdonaldjames placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT bammlertheo placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT daydrewb placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT loftuschristinet placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT kannankurunthachalam placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT masonwalex placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT bushnicoler placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT lewinnkajaz placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT enquobahriedaniela placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT marsitcarmen placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons AT sathyanarayanasheela placentaltranscriptomicsignaturesofprenatalexposuretohydroxypolycyclicaromatichydrocarbons |