The effect of hypoxia in development

Abstract

There is increasing evidence that the oxygen supply to the human embryo in the first trimester is tightly controlled, suggesting that too much oxygen may interfere with development. The use of hypoxia probes in mammalian embryos during the organogenic period indicates that the embryo is normally in a state of partial hypoxia, and this may be essential to control cardiovascular development, perhaps under the control of hypoxia-inducible factor (HIF). A consequence of this state of partial hypoxia is that disturbances in the oxygen supply can more easily lead to a damaging degree of hypoxia. Experimental mammalian embryos show a surprising degree of resilience to hypoxia, with many organogenic stage embryos able to survive 30-60 min of anoxia. However, in some embryos this degree of hypoxia causes abnormal development, particularly transverse limb reduction defects. These abnormalities are preceded by hemorrhage/edema and tissue necrosis. Other parts of the embryo are also susceptible to this hypoxia-induced damage and include the genital tubercle, the developing nose, the tail, and the central nervous system. Other frequently observed defects in animal models of prenatal hypoxia include cleft lip, maxillary hypoplasia, and heart defects. Animal studies indicate that hypoxic episodes in the first trimester of human pregnancy could occur by temporary constriction of the uterine arteries. This could be a consequence of exposure to cocaine, misoprostol, or severe shock, and there is evidence that these exposures have resulted in hypoxia-related malformations in the human. Exposure to drugs that block the potassium current (IKr) can cause severe slowing and arrhythmia of the mammalian embryonic heart and consequently hypoxia in the embryo. These drugs are highly teratogenic in experimental animals. There is evidence that drugs with IKr blockade as a side effect, for example phenytoin, may cause birth defects in the human by causing periods of embryonic hypoxia. The strongest evidence of hypoxia causing birth defects in the human comes from studies of fetuses lacking hemoglobin (Hb) F. These fetuses are thought to be hypoxic from about the middle of the first trimester and show a range of birth defects, particularly transverse limb reduction defects. Birth Defects Research (Part C) 81: [215][216][217][218][219][220][221][222][223][224][225][226][227][228] 2007. V C 2007 Wiley-Liss, Inc.

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

“…Both lack and surplus of oxygen are deleterious for normal development, and oxygen tension is tightly regulated in the embryo (Webster and Abela, 2007). Mammalian embryos are fairly well equipped to survive short periods of hypoxia or anoxia, but even such brief exposures can cause a spectrum of developmental defects (transverse limb reductions, face and heart malformations; reviewed in Webster et al, 2007). Hypoxia is a stimulus for both embryonic and adult angiogenesis, and together with hemodynamics the main factor directing development and patterning of the cardiovascular system (Ribatti, 2006).…”

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

“…These hypoxic areas change depending upon the age of the fetus (Webster & Abela, 2007). Pimonidazole also co-localises with cardiac developmental markers including vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF-1α).…”

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

“…First studies on a narrow range of selected diseases suggest that maternal asthma during pregnancy is associated with an increased risk of asthma, 7,8 bronchiolitis, 9 atopic dermatitis, 10 and autism spectrum disorder 11 in the offspring during childhood, which is in line with animal models documenting intrauterine susceptibility to hypoxia-induced damage. 12 These findings, together with the high prevalence of maternal asthma during pregnancy, make it important to further put a focus on follow-up time extended beyond the perinatal period and to cover a larger spectrum of offspring diseases.The purpose of this study was to assess the associations between asthma during pregnancy and the offspring's risk of a wide range of diseases, categorized according to major chapters of the International Classification of Diseases, 10th Revision (ICD-10), during early childhood. …”