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PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in...

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Autores principales: Li, Shuxian, Li, Lingbing, Zhang, Changqing, Fu, Huaxuan, Yu, Shuping, Zhou, Meijuan, Guo, Junjun, Fang, Zhenya, Li, Anna, Zhao, Man, Zhang, Meihua, Wang, Xietong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584374/
https://www.ncbi.nlm.nih.gov/pubmed/37737576
http://dx.doi.org/10.7554/eLife.85944
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author Li, Shuxian
Li, Lingbing
Zhang, Changqing
Fu, Huaxuan
Yu, Shuping
Zhou, Meijuan
Guo, Junjun
Fang, Zhenya
Li, Anna
Zhao, Man
Zhang, Meihua
Wang, Xietong
author_facet Li, Shuxian
Li, Lingbing
Zhang, Changqing
Fu, Huaxuan
Yu, Shuping
Zhou, Meijuan
Guo, Junjun
Fang, Zhenya
Li, Anna
Zhao, Man
Zhang, Meihua
Wang, Xietong
author_sort Li, Shuxian
collection PubMed
description Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.
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spelling pubmed-105843742023-10-19 PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis Li, Shuxian Li, Lingbing Zhang, Changqing Fu, Huaxuan Yu, Shuping Zhou, Meijuan Guo, Junjun Fang, Zhenya Li, Anna Zhao, Man Zhang, Meihua Wang, Xietong eLife Cell Biology Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies. eLife Sciences Publications, Ltd 2023-09-22 /pmc/articles/PMC10584374/ /pubmed/37737576 http://dx.doi.org/10.7554/eLife.85944 Text en © 2023, Li, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Li, Shuxian
Li, Lingbing
Zhang, Changqing
Fu, Huaxuan
Yu, Shuping
Zhou, Meijuan
Guo, Junjun
Fang, Zhenya
Li, Anna
Zhao, Man
Zhang, Meihua
Wang, Xietong
PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title_full PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title_fullStr PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title_full_unstemmed PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title_short PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
title_sort pm2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via klf9/cyp1a1 transcriptional axis
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584374/
https://www.ncbi.nlm.nih.gov/pubmed/37737576
http://dx.doi.org/10.7554/eLife.85944
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