Nutrition is the major intrauterine environmental factor that alters expression of the fetal genome and may have lifelong consequences. This phenomenon, termed “fetal programming,” has led to the recent theory of fetal origins of adult disease. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, and metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine, and cardiovascular diseases in adult life. Animal studies show that both maternal undernutrition and over nutrition reduce placental-fetal blood flows and stunt fetal growth. Impaired placental syntheses of nitric oxide, a major vasodilator and angiogenesis factor, and polyamines, key regulators of DNA and protein synthesis, may provide a unified explanation for intrauterine growth retardation in response to the 2 extremes of nutritional problems with the same pregnancy outcome. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the impact of maternal nutrition on both fetal programming and genomic imprinting. Promoting optimal nutrition will not only ensure optimal fetal development, but will also reduce the risk of chronic diseases in adults.
Maternal nutrition plays a critical role in fetal growth and development. Although considerable effort has been directed towards defining nutrient requirements of animals over the past 30 y, suboptimal nutrition during gestation remains a significant problem for many animal species (e.g., cattle, pigs, and sheep) worldwide. Despite advanced prenatal care for mothers and fetuses, ∼5% of human infants born in the U.S. suffer from intrauterine growth retardation. Over the past decade, compelling epidemiological studies have linked IUGR with the etiology of many chronic diseases in adult humans and animals. These intriguing findings have prompted extensive animal studies to identify the biochemical basis for nutritional programming of fetal development and its long-term health consequences. This article reviews the recent advances in this emerging area of research. Multiple genetic and environmental factors contribute to IUGR. Although the fetal genome plays an important role in growth potential in utero, increasing evidence suggests that the intrauterine environment is a major determinant of fetal growth. For example, embryo-transfer studies show that it is the recipient mother rather than the donor mother that more strongly influences fetal growth. There is also evidence that the intrauterine environment of the individual fetus may be of greater importance in the etiology of chronic diseases in adults than the genetics of the fetus. For instance, in twin pregnancies, a baby with fetal growth retardation is more likely to develop noninsulin dependent (type-II) diabetes mellitus than a sibling with normal fetal growth. Among intrauterine environmental factors, nutrition plays the most critical role in influencing placental and fetal growth.
IUGR causes both perinatal and neonatal medical complications. For example, IUGR is responsible for about 50% of normal formed stillbirths in humans. Infants who weigh <2.5 kg at birth have perinatal mortality rates that are 5 to 30 times greater than those of infants who have average birth weights, while those <1.5 kg have rates 70 to 100 times greater. Surviving infants with IUGR are often at increased risk for neurological, respiratory, intestinal, and circulatory disorders during the neonatal period. Both epidemiological and experimental evidence suggest that IUGR contributes to a wide array of metabolic disorders and chronic diseases in adults. For example, individuals exposed to the Dutch winter famine of 1944–1945 in utero had higher rates of insulin resistance, vascular disease, morbidity, and mortality in adulthood. A cohort study of 15,000 Swedish men and women born between 1915 and 1929 provides by far the most convincing evidence for the close association between reduced fetal growth rate and increased risk of death from ischemic heart disease. Thus, the intrauterine environment of the conceptus may alter expression of the fetal genome and have lifelong consequences. This phenomenon is termed “fetal programming,” which has led to the recent theory of “fetal origins of adult disease”. Namely, alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology and metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine, and cardiovascular diseases in adult life.
References:
Guoyao Wu, Fuller W. Bazer, Timothy A. Cudd, Cynthia J. Meininger, Thomas E. Spencer; Maternal Nutrition and Fetal Development, The Journal of Nutrition, Volume 134, Issue 9, 1 September 2004, Pages 2169–2172, https://doi.org/10.1093/jn/134.9.2169
Parul Christian, Christine P. Stewart; Maternal Micronutrient Deficiency, Fetal Development, and the Risk of Chronic Disease, The Journal of Nutrition, Volume 140, Issue 3, 1 March 2010, Pages 437–445
Lorraine Gambling, Ruth Danzeisen, Cedric Fosset, Henriette S. Andersen, Susan Dunford, S. Kaila S. Srai, Harry J. McArdle; Iron and Copper Interactions in Development and the Effect on Pregnancy Outcome, The Journal of Nutrition, Volume 133, Issue 5, 1 May 2003, Pages 1554S–1556S