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This chapter reviews the key roles of the different layers of the maternofetal interface in supplying essential nutrients to the developing fetus before the placental circulations are fully established. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes that remodel the uteroplacental interface. The distribution of the placental-specific protein human chorionic gonadotrophin (hCG) in yolk sac and coelomic fluid samples, and the absence of hCG mRNA expression in yolk sac tissue, suggests the secondary yolk sac (SYS) has an absorptive function. During the 10th week of gestation, the yolk sac starts to degenerate and rapidly ceases to function. The anatomy of the materno-fetal interface in the first trimester is the result of the need for a delicate balance between the metabolic requirements of the developing fetus and the potential harmful effects of oxygen during embryogenesis and organogenesis.