Hypoxia: From Placental Development to Fetal Programming

Abstract

Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc.

Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

“…Intrauterine hypoxia is one of the most significant complications during pregnancy, challenging normal fetal growth and development (6,27,33). The hypoxemic fetus adapts to its environment by redistributing its cardiac output (CO) to critical organs of need, such as the heart, brain, and adrenal glands (60,62,65,66), resulting in asymmetric fetal growth restriction.…”

Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys

“…Hypoxia plays an important role in various processes during fetal development, like placentation, angiogenesis, and hematopoiesis [ 1 ]. Renal development is also driven by low partial oxygen pressure, which in the rat initiates after the implantation and the apparition of the primitive streak, around gestational day (GD) 8 or 9 [ 2 ].…”

“…HIF-1 is responsible for the activation of over 60 genes that encode for growth factors, glucose transporters, transcription factors, erythropoietin, etc. In that manner, HIF-1 modulates oxygen consumption, cell survival, anaerobic metabolism, growth and development, and cell proliferation under hypoxic conditions [ 1 , 4 ].…”

Hypoxia in the Initiation and Progression of Neuroblastoma Tumours

“…Deregulation of blood oxygen levels during embryonic development can interfere with neural crest-derived tissue maturation. The relevance of hypoxic events during normal embryonic and foetal development affecting placentation, angiogenesis and haematopoiesis has been widely described [18,19]. Hypoxia regulates the amount of neural crest migrating cells in a chick embryo model [20].…”