Placental development begins soon after fertilization. The fertilized ovum undergoes several cell divisions, forming a morula by about day three, which further develops into a blastocyst by day four to five after fertilization. As the blastocyst reaches the uterine lining, it begins implantation into the uterine decidua around day six to seven. At this stage, the blastocyst differentiates into two primary structures: the trophoblast and the embryoblast. The trophoblast cells further differentiate into syncytiotrophoblasts and cytotrophoblasts, which form the fetal component of the placenta. The syncytiotrophoblasts are multinucleated cells that penetrate deep into the maternal endometrium, while the cytotrophoblasts reside closer to the inner layers. Together, these cells anchor the placenta to the maternal uterine wall and create a villous tree structure, which facilitates the exchange of substances between mother and fetus.
As pregnancy progresses, the villous structure of the placenta undergoes several changes to optimize the distance between maternal blood and fetal vessels, thereby enhancing maternal-fetal exchanges. The placenta evolves from having early-stage mesenchymal villi in the first trimester to having terminal villi, which appear from about 27 weeks and predominate in the third trimester, where most nutrient and gas exchange takes place. The terminal villi are crucial to the functioning of the placenta as the main site for maternal-fetal exchange, allowing the passage of oxygen, nutrients, and waste products between maternal and fetal circulations. The numbers behind this remodeling matter for drug transfer: the diffusion distance between maternal and fetal blood shrinks from 50 to 100 micrometers in the first trimester to 4 to 5 micrometers at term, while the villous surface area grows to roughly 11 to 13 square meters. The term placenta is a disc 15 to 20 cm across and 2 to 3 cm thick, weighing about 500 g, roughly one sixth of the fetal weight.
