High-altitude hypoxia and preeclampsia.
The influence of hypoxia (lowered arterial blood and/or tissue PO2) on fetoplacental development and the role of hypoxia in preeclampsia are major research foci in perinatal biology. While animal and cell models are of utility, we do not know whether artificial hypoxic stimuli mimic the pathological conditions attributed to hypoxic stress in vivo; we cannot distinguish the effects of hypoxia from under- or overlying pathologies. High altitude (>2700 m) is the natural experiment we can use to distinguish pathology from adaptation in human pregnancy. The two best known impacts of high altitude on pregnancy outcome are reduced fetal growth and an increased incidence preeclampsia. This review focuses on the mechanisms by which altitude increases maternal risk for the development of preeclampsia. The review first considers the evidence that placental hypoxia is causally involved in the development of preeclampsia. It then focuses on how data from studies of pregnant women at high altitude support (or do not support) etiological models of preeclampsia. Considered are the theories that reduced uteroplacental blood flow, circulating factors of placental origin, placental oxidative stress and increased maternal vascular reactivity are etiological in preeclampsia. The data suggest that oxidative stress and endothelial dysfunction have pathophysiological origins that are independent of placental hypoxia. We conclude that altitude shifts the individual risk for the development of preeclampsia because of impacts on multiple physiological systems, no one of which can be specifically pointed to as causal.
Zamudio
Stacy
S
Dept. of Obstetrics, Gynecology and Women's Health, UMD-New Jersey Medical School, Newark, NJ 07103-2714, USA. stacy.Zamudio@UMDNJ.edu
D000532:Altitude Sickness / Q000150:complications* / Q000503:physiopathology; D001775:Blood Circulation; D005260:Female; D006801:Humans; D018384:Oxidative Stress; D010920:Placenta / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy