The Placental Exposome: Placental Determinants of Fetal Adiposity and Postnatal Body Composition

Abstract

Offspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placental function. High plasma levels of particular nutrients in obese and diabetic mothers are likely to be the important drivers of nutrient transfer to the fetus, resulting in excess fat accretion. However, not all offspring of obese and diabetic mothers are born large for gestational age and the explanation may involve the regulation of placental nutrient transfer required for fetal growth. The placenta integrates maternal and fetal signals across gestation in order to determine nutrient transfer rate. Understanding the nature of these signals and placental responses to them is key to understanding the pathology of both fetal growth restriction and macrosomia. The overall effects of the maternal environment on the placenta are the product of its exposures throughout gestation, the ‘placental exposome'. Understanding these environmental influences is important as exposures early in gestation, for instance causing changes in the function of genes involved in nutrient transfer, may determine how the placenta will respond to exposures later in gestation, such as to raised maternal plasma glucose or lipid concentrations. Longitudinal studies are required which allow investigation of the influences on the placenta across gestation. These studies need to make full use of developing technologies characterising placental function, fetal growth and body composition. Understanding these processes will assist in the development of preventive strategies and treatments to optimise prenatal growth in those pregnancies at risk of either excess or insufficient nutrient supply and could also reduce the risk of chronic disease in later life.

Morphomics: An integral part of systems biology of the human placenta

“…In the placenta, it has been studied in the context of fetal adiposity and postnatal body composition [35].…”

Type 1, type 2 and gestational diabetes mellitus differentially impact placental pathologic characteristics of uteroplacental malperfusion

“…Nonetheless, the maternal-placental and fetal-placental circulations exchange blood at the terminal villi. Maternal complications of pregnancy, such as maternal diabetes (2), and fetal morbidities, including stillbirth (3) and fetal growth abnormalities (3, 4), have been significantly associated with placental vascular abnormalities. However, the association of placental vascular abnormalities with various diabetes types has not been well elucidated; therefore, an enhanced understanding of the effect of maternal diabetes on placental pathology and, specifically, placental vasculature is warranted.…”

The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development

“…The placenta is able to respond to maternal and fetal environmental exposures ("placental exposome") in growth and development (84,86), as supported, for example, by alterations in both methylation and expression of human placental glucose transport across pregnancy (105). The independent phenotypic traits of the placenta itself have predictive value for the offspring outcome.…”