This chapter reviews the roles and distribution of O2 inside the early human gestational sac and its impact on our understanding of the physiology of O2 metabolism by the fetus during the first and early second trimesters of pregnancy. The mammalian fetus is exposed to major fluctuations in O2 concentration from conception to delivery. The first trimester gestational sac has additional barriers to materno-fetal exchange compared to the definitive placenta of the second and third trimesters of pregnancy. Ample dilation of the uteroplacental circulation together with rapid villous angiogenesis are the key factors necessary to adequate placental development and function and subsequent fetal growth. Overall the data have confirmed that the human placenta is not truly hemochorial until the end of the first trimester. Rather it is deciduochorial, being supported by tissue fluids and endometrial secretions.

Placental nutrient transfer capacity increases over gestation by increased placental growth, primarily of membrane surface area, allowing for the increase in nutrient supply required for the growing fetus. Glucose is the primary energy substrate for the mammalian fetus and placenta. The fetus metabolizes glucose in several ways, including oxidation for energy requirements and as a carbon source for production of various macromolecules, such as glycogen, glycolytic products, proteins, and fatty acids. Total nitrogen concentration measurements have been used to estimate the rate of protein accretion in tissues, because most of the total nitrogen is represented by amino acid nitrogen uptake. The net uptake of amino acids by umbilical circulation through the placenta represents the dietary supply of amino acids for fetal growth and protein metabolism. The transport of fatty acids and other lipid substances across the placenta and the deposition of lipids in fetal adipose tissue are primarily late-gestation phenomena.