PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis.
CYP1A1
KLF9
cell biology
cyp1a1
fine particulate matter
klf9
mitochondrial apoptosis
oxidative stress
trophoblast
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
22 09 2023
22 09 2023
Historique:
received:
04
01
2023
accepted:
21
09
2023
medline:
23
10
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 37737576
doi: 10.7554/eLife.85944
pii: 85944
pmc: PMC10584374
doi:
pii:
Substances chimiques
Cytochrome P-450 CYP1A1
EC 1.14.14.1
KLF9 protein, human
0
Kruppel-Like Transcription Factors
0
CYP1A1 protein, human
EC 1.14.14.1
Banques de données
GEO
['GSE237795']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023, Li, Li et al.
Déclaration de conflit d'intérêts
SL, LL, CZ, HF, SY, MZ, JG, ZF, AL, MZ, MZ, XW No competing interests declared
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