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Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion
BACKGROUND: Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400245/ https://www.ncbi.nlm.nih.gov/pubmed/35999615 http://dx.doi.org/10.1186/s13148-022-01327-2 |
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author | Zhu, Weiqiang Gu, Yan Li, Min Zhang, Zhaofeng Liu, Junwei Mao, Yanyan Zhu, Qianxi Zhao, Lin Shen, Yupei Chen, Fujia Xia, Lingjin He, Lin Du, Jing |
author_facet | Zhu, Weiqiang Gu, Yan Li, Min Zhang, Zhaofeng Liu, Junwei Mao, Yanyan Zhu, Qianxi Zhao, Lin Shen, Yupei Chen, Fujia Xia, Lingjin He, Lin Du, Jing |
author_sort | Zhu, Weiqiang |
collection | PubMed |
description | BACKGROUND: Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollution exposure. We compared data of decidual tissue from individuals with induced abortions and those with RSA by bulk RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq). Differentially expressed genes (DEGs) were verified using RT-qPCR and pyrosequencing. A logistic regression model was used to investigate the association between air pollutants exposure and RSA. RESULTS: We identified 98 DEGs with aberrant methylation by overlapping the RRBS and RNA-seq data. Nineteen immune cell subsets were identified. Compared with normal controls, NK cells and macrophages accounted for different proportions in the decidua of patients with RSA. We observed that the methylation and expression of IGF2BP1 were different between patients with RSA and controls. Furthermore, we observed significant positive associations between maternal air pollutants exposure during the year prior to pregnancy and in early pregnancy and the risk of RSA. Mediation analyses suggested that 24.5% of the effects of air pollution on the risk of RSA were mediated through IGF2BP1 methylation. CONCLUSION: These findings reveal a comprehensive cellular and molecular mechanism of RSA and suggest that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01327-2. |
format | Online Article Text |
id | pubmed-9400245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94002452022-08-25 Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion Zhu, Weiqiang Gu, Yan Li, Min Zhang, Zhaofeng Liu, Junwei Mao, Yanyan Zhu, Qianxi Zhao, Lin Shen, Yupei Chen, Fujia Xia, Lingjin He, Lin Du, Jing Clin Epigenetics Research BACKGROUND: Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollution exposure. We compared data of decidual tissue from individuals with induced abortions and those with RSA by bulk RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq). Differentially expressed genes (DEGs) were verified using RT-qPCR and pyrosequencing. A logistic regression model was used to investigate the association between air pollutants exposure and RSA. RESULTS: We identified 98 DEGs with aberrant methylation by overlapping the RRBS and RNA-seq data. Nineteen immune cell subsets were identified. Compared with normal controls, NK cells and macrophages accounted for different proportions in the decidua of patients with RSA. We observed that the methylation and expression of IGF2BP1 were different between patients with RSA and controls. Furthermore, we observed significant positive associations between maternal air pollutants exposure during the year prior to pregnancy and in early pregnancy and the risk of RSA. Mediation analyses suggested that 24.5% of the effects of air pollution on the risk of RSA were mediated through IGF2BP1 methylation. CONCLUSION: These findings reveal a comprehensive cellular and molecular mechanism of RSA and suggest that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01327-2. BioMed Central 2022-08-23 /pmc/articles/PMC9400245/ /pubmed/35999615 http://dx.doi.org/10.1186/s13148-022-01327-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhu, Weiqiang Gu, Yan Li, Min Zhang, Zhaofeng Liu, Junwei Mao, Yanyan Zhu, Qianxi Zhao, Lin Shen, Yupei Chen, Fujia Xia, Lingjin He, Lin Du, Jing Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title | Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title_full | Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title_fullStr | Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title_full_unstemmed | Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title_short | Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
title_sort | integrated single-cell rna-seq and dna methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400245/ https://www.ncbi.nlm.nih.gov/pubmed/35999615 http://dx.doi.org/10.1186/s13148-022-01327-2 |
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