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Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
AL. Fisher, V. Sangkhae, K. Balušíková, NJ. Palaskas, T. Ganz, E. Nemeth
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
R01 HD096863
NICHD NIH HHS - United States
T32 GM065823
NIGMS NIH HHS - United States
UL1 TR000124
NCATS NIH HHS - United States
F31 HD097931
NICHD NIH HHS - United States
UL1 TR001881
NCATS NIH HHS - United States
NLK
Directory of Open Access Journals
od 2015
Free Medical Journals
od 2010
Nature Open Access
od 2010-12-01
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2010-01-01
Open Access Digital Library
od 2015-01-01
Open Access Digital Library
od 2015-01-01
Medline Complete (EBSCOhost)
od 2012-11-01
Health & Medicine (ProQuest)
od 2010-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2010
Springer Nature OA/Free Journals
od 2010-12-01
- MeSH
- apoptóza fyziologie MeSH
- embryo savčí patologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- ferritiny analýza MeSH
- hepcidiny genetika MeSH
- komplikace těhotenství MeSH
- kultivované buňky MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- obezita patologie MeSH
- placenta patologie MeSH
- těhotenství MeSH
- TNF-alfa metabolismus MeSH
- železo metabolismus toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.
Citace poskytuje Crossref.org
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