The Programming Power of the Placenta

Abstract

Size at birth is a critical determinant of life expectancy, and is dependent primarily on the placental supply of nutrients. However, the placenta is not just a passive organ for the materno-fetal transfer of nutrients and oxygen. Studies show that the placenta can adapt morphologically and functionally to optimize substrate supply, and thus fetal growth, under adverse intrauterine conditions. These adaptations help meet the fetal drive for growth, and their effectiveness will determine the amount and relative proportions of specific metabolic substrates supplied to the fetus at different stages of development. This flow of nutrients will ultimately program physiological systems at the gene, cell, tissue, organ, and system levels, and inadequacies can cause permanent structural and functional changes that lead to overt disease, particularly with increasing age. This review examines the environmental regulation of the placental phenotype with particular emphasis on the impact of maternal nutritional challenges and oxygen scarcity in mice, rats and guinea pigs. It also focuses on the effects of such conditions on fetal growth and the developmental programming of disease postnatally. A challenge for future research is to link placental structure and function with clinical phenotypes in the offspring.

Keywords: fetus; maternal environment; nutrient transport; placenta; pregnancy; programming.

Figure 1

The effect of an environmental challenge, such as maternal nutrient manipulation or oxygen scarcity, on placental phenotype, fetal growth, and offspring outcome. The placenta can adapt morphologically and functionally to optimize substrate supply and fetal growth in the face of an environmental challenge. While these adaptations may meet the fetal drive for growth, they alter the amount and relative proportions of specific metabolic substrates supplied to the fetus during development. This will ultimately program physiological systems at the gene, cell, tissue, organ, and system levels and cause permanent structural and functional changes, leading to overt disease in adulthood, particularly with increasing age.