Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling, and congenital heart defects
Por:
Olive, EL, Xiao, E, Natale, DR, Fisher, SA
Publicada:
1 dic 2018
Resumen:
Low oxygen concentration (hypoxia) is part of normal embryonic development, yet the situation is complex. Oxygen (O-2) is a janus gas with low levels signaling through hypoxia-inducible transcription factor (HIF) that are required for development of fetal and placental vasculature and fetal red blood cells. This results in coupling of fetus and mother around midgestation as a functional feto-placental unit (FPU) for O-2 transport, which is required for continued growth and development of the fetus. Defects in these processes may leave the developing fetus vulnerable to O-2 deprivation or other stressors during this critical midgestational transition when common septal and conotruncal heart defects (CHDs) are likely to arise. Recent human epidemiological and case-control studies support an association between placental dysfunction, manifest as early onset pre-eclampsia (PE) and increased serum bio-markers, and CHD. Animal studies support this association, in particular those using gene inactivation in the mouse. Sophisticated methods for gene inactivation, cell fate mapping, and a quantitative bio-reporter of O-2 concentration support the premise that hypoxic stress at critical stages of development leads to CHD. The secondary heart field contributing to the cardiac outlet is a key target, with activation of the un-folded protein response and abrogation of FGF signaling or precocious activation of a cardiomyocyte transcriptional program for differentiation, suggested as mechanisms. These studies provide a strong foundation for further study of feto-placental coupling and hypoxic stress in the genesis of human CHD.
Filiaciones:
Olive, EL:
Univ Autonoma Barcelona, St Pau Univ Hosp, Dept Obstet & Gynecol, Barcelona, Spain
Inst Hlth Carlos III, Maternal & Child Hlth & Dev Network II SAMID II R, Madrid, Spain
Xiao, E:
Univ Maryland, Sch Med, Dept Med, S-012a HSF2 20 Penn St, Baltimore, MD 21201 USA
Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA
Natale, DR:
Univ Calif San Diego, Dept Obstet & Gynecol & Reprod Sci, San Diego, CA 92103 USA
Fisher, SA:
Univ Maryland, Sch Med, Dept Med, S-012a HSF2 20 Penn St, Baltimore, MD 21201 USA
Univ Maryland, Sch Med, Dept Physiol & Biophys, Baltimore, MD 21201 USA
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