PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
- Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, China
- Shandong University Cheeloo College of Medicine, China
- Jinan Environmental Monitoring Center of Shandong Province, China
Abstract
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 number 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.
Data availability
The RNA sequencing data were deposited into the Gene Expression Omnibus (GEO) database (accession number: GSE237795)
Article and author information
Author details
Funding
Scientific Research Project of Maternal and Child Health Care Hospital of Shandong Province (NO. YJKY2022-024)
- Shuxian Li
The funders did the experiment and drafted the article in this study d.
Reviewing Editor
- Marisa Nicolás, Laboratório Nacional de Computação Científica, Brazil
Ethics
Animal experimentation: The experimental design is in accordance with the principles of animal protection, experimental animal welfare ethics and other ethical requirements, Applicants are committed to abide by the relevant experimental animal ethics, and accept the supervision and inspection of the Committee at any time. Experiment related personnel qualification and experiment related units are appropriate. Varieties, quality grade and specifications of animals used in experiments are appropriate.Research Ethics Committee approval of Maternal and Child Healthcare Hosnital of Shandong ProvinceApproval Number:2021-116
Human subjects: The qualification and experience of researcher meet the test requirements; the research project is accordance with the scientific and ethical principles; the method of obtaining informed consent is right.The study was approved by the Research Ethics Committee approval of Maternal and Child Healthcare Hospital of Shandong ProvinceApproval Number:2020-115
Version history
- Received: January 4, 2023
- Accepted: September 21, 2023
- Accepted Manuscript published: September 22, 2023 (version 1)
- Version of Record published: October 18, 2023 (version 2)
- Version of Record updated: March 26, 2024 (version 3)
Copyright
© 2023, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis
eLife 12:e85944.
https://doi.org/10.7554/eLife.85944
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