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334562 
Journal Article 
Early fetal hypoxia leads to growth restriction and myocardial thinning 
Ream, M; Ray, AM; Chandra, R; Chikaraishi, DM 
2008 
Yes 
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
ISSN: 0363-6119
EISSN: 1522-1490 
64 
2 
Hypoxia is necessary for fetal development; however, excess hypoxia is detrimental. Hypoxia has been extensively studied in the near-term fetus, but less is known about earlier fetal effects. The purpose of this study was to determine the window of vulnerability to severe hypoxia, what organ system(s) is most sensitive, and why hypoxic fetuses die. We induced hypoxia by reducing maternal-inspired O[sup]2[/sup] from 21% to 8%, which decreased fetal tissue oxygenation assessed by pimonidazole binding. The mouse fetus was most vulnerable in midgestation: 24 h of hypoxia killed 89% of embryonic day 13.5 (E13.5) fetuses, but only 5% of E11.5 and 51% of E17.5 fetuses. Sublethal hypoxia at E12.5 caused growth restriction, reducing fetal weight by 26% and protein by 45%. Hypoxia induced HIF-1 target genes, including vascular endothelial growth factor (Vegf), erythropoietin, glucose transporter-1 and insulin-like growth factor binding protein-1 (Igfbp-1), which has been implicated in human intrauterine growth restriction (IUGR). Hypoxia severely compromised the cardiovascular system. Signs of heart failure, including loss of yolk sac circulation, hemorrhage, and edema, were caused by 18-24 h of hypoxia. Hypoxia induced ventricular dilation and myocardial hypoplasia, decreasing ventricular tissue by 50% and proliferation by 21% in vivo and by 40% in isolated cultured hearts. Epicardial detachment was the first sign of hypoxic damage in the heart, although expression of epicardially derived mitogens, such as FGF2, FGF9, and Wnt9b was not reduced. We propose that hypoxia compromises the fetus through myocardial hypoplasia and reduced heart rate. (English) 
epicardium; myocardium; hypoxia-inducible transcription factor-1; human intrauterine growth restriction; insulin-like growth factor binding protein-1; Oxygène; Homme; Souris; Facteur transcription HIF1; Protéine liaison IGFBP; Embryon; Oxygénation; Tissu; Vulnérabilité; Développement; Croissance; Plomb; Hypoxie; Foetus; Précoce; Vertebrata; Mammalia; Rodentia; Appareil circulatoire; Cardiopathie; Pathologie de lappareil circulatoire; Métal lourd; Oxygen; Human; Mouse; Transcription factor HIF1; Insulin like growth factor binding protein; Embryo; Oxygenation; Tissue; Vulnerability; Development; Growth; Lead; Hypoxia; Fetus; Early; Circulatory system; Heart disease; Cardiovascular disease; Heavy metal; Oxígeno; Hombre; Ratón; Factor transcripción HIF1; Proteína enlace IGFBP; Embrión; Oxigenación; Tejido; Vulnerabilidad; Desarrollo; Crecimiento; Plomo; Hipoxia; Feto; Precoz; Aparato circulatorio; Cardiopatía; Aparato circulatorio patología; Metal pesado