Embryonic and fetal programming of physiological disorders in adulthood.
In the past decade, data from numerous epidemiological studies have indicated strong inverse associations between birth weight and risk of coronary heart disease, hypertension, type 2-diabetes, and other diseases in adulthood. The "Barker hypothesis" thus postulates that a number of organ structures and functions undergo programming during embryonic and fetal life. This developmental programming determines the set points of physiological and metabolic responses in adult life. Alterations of nutrient availability during gestation may lead to developmental adaptations, via hormonal maneuvers by the embryo and fetus that readjust these set points. These adaptive measures have short-term benefits to the embryo and fetus, so that the newborn will be better prepared for the adverse environment (e.g., undernutrition). However, adequate nutritional support during postnatal life that enables catch-up growth may create metabolic conflicts that predispose the adult to aberrant physiological functions and, ultimately, increased risk of disease. It is plausible that other adverse in utero conditions, including exposure to developmental toxicants, may similarly alter adult disease susceptibility. This article provides an overview of the Barker hypothesis, its supporting evidence, the current advances in understanding the biological mechanisms underlying this phenomenon, and its implications for developmental toxicology.
Lau
Christopher
C
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. lau.christopher@epa.gov
Rogers
John M
JM
D000818:Animals; D001724:Birth Weight / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology*; D015509:Developmental Biology / Q000639:trends; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects; D008659:Metabolic Diseases / Q000209:etiology*; D008954:Models, Biological; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D014116:Toxicology / Q000639:trends