Hypoxia and Fetal Heart Development

Abstract

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts

“…The effect of hypoxia on fibroblasts is attenuated by UDCA A fetus develops in a state of partial hypoxia during pregnancy (Clancy et al, 2007;Patterson and Zhang, 2010;Webster and Abela, 2007). Therefore, further investigation into the effect of hypoxia on neonatal rat and human fetal fibroblasts was carried out.…”

Graduated effects of high-altitude hypoxia and highland ancestry on birth size

“…Of note, multigenerational highaltitude populations demonstrate protection against the effects of high-altitude hypoxia on fetal growth (14)(15)(16)(17)(18). Experimental studies in animal models support the likelihood that prenatal hypoxia can program cardiac, vascular, and metabolic dysfunction in the adult offspring (19)(20)(21), and that high-altitude ancestry protects against the effect of chronic hypoxic development on fetal growth (22).…”

Changes in the Contractile Cardiomyocytes and Hemomicrocirculatory Bed in Pregnant Rats and Their Pups Exposed to Hemic Hypoxia

“…В современных условиях течение беременности во многом зависит от воз-растающей частоты воздействия на орга-низм беременной неблагоприятных экзо-генных факторов [4,9]. В связи с тем, что биологическое действие большинства неблагоприятных факторов реализуется в виде различных заболеваний, развиваю-щихся в течение беременности и связан-ных с недостатком кислорода в тканях матери и плода, реакция системы мать-плацента-плод на гемическую гипоксию представляет особый интерес.…”

“…[1,2]. Не вызывает сомнения тот факт, что истоки многих хронических, инвалидизирующих или фатальных патологических состояний у взрослых, в том числе заболеваний сер-дечно-сосудистой системы, берут начало в антенатальном периоде и представляют собой пролонгированную патологию пло-да [6,8,9]. Известно, что гипоксия плода приводит к нарушению вегетативной ре-гуляции коронарных сосудов, ухудшению энергетического обмена с резким умень-шением образования макроэргических соединений в митохондриях кардиомио-цитов и клеток синусового узла [5,10].…”