Placental adaptive responses and fetal programming.
Fetal programming occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or 'insult' applied at a critical point in in utero development. This then leads to an effect, for example diabetes or hypertension, which manifests itself in adult life. As the placenta is the regulator of nutrient composition and supply from mother to fetus and the source of hormonal signals that affect maternal and fetal metabolism, appropriate development of the placenta is crucial to normal fetal development. Placental function evolves in a carefully orchestrated developmental cascade throughout gestation. Disruption of this cascade can lead to abnormal development of the placental vasculature or of the trophoblast. Timing of a developmental 'insult' will be critical in consequent placental function and hence programming of the fetus. The 'insults' that alter placental development include hypoxia and abnormal maternal nutrient status, to which the placenta may adapt by alterations in transporter expression and activity to maintain fetal growth or by epigenetic regulation of placental gene expression. Hypoxia is physiological for organogenesis and placental tissue normally exists in a relatively hypoxic environment, but intrauterine growth restriction (IUGR) and pre-eclampsia are associated with a greater degree of trophoblast hypoxia. The metabolic activity of placental mitochondria leads to oxidative stress even in normal pregnancy which is exacerbated further in IUGR, diabetic and pre-eclamptic pregnancies and may also give nitrative stress known to lead to covalent modification and hence altered activity of proteins. Hypoxia, oxidative and nitrative stress all alter placenta development and may be a general underlying mechanism that links altered placental function to fetal programming.
Myatt
Leslie
L
Department of Obstetrics and Gynecology, University of Cincinnati, College of Medicine, PO Box 670526, Cincinnati, OH 45267, USA. leslie.myatt@uc.edu
D000222:Adaptation, Physiological / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000502:physiology*; D021041:Placental Circulation / Q000502:physiology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*