Development of the placenta is a highly regulated process that is essential for normal fetal growth and development, and for maintenance of a healthy pregnancy. The placenta fulfills several critical roles as the interface between mother and fetus: it prevents rejection of the fetal allograft, enables respiratory gas exchange, transports nutrients, eliminates fetal waste products, and secretes peptide and steroid hormones.
Implantation and invasion — Development of the placenta and fetus is a continuous process that begins at the time of fertilization. The first three days of development occur within the fallopian tube. Four days after fertilization, the morula (a solid mass of blastomere cells) enters the uterus. On the fifth day after fertilization, the morula becomes a blastocyst as fluid accumulates and polarization of the cells occurs. The blastocyst has an outer layer of cells (trophoblast) that will form the placenta and fetal membranes, an inner cell mass at one pole that will form the embryo, and a fluid filled cavity. The inner and outer cell masses multiply and the fluid cavity enlarges until the expanded blastocyst hatches out of the zona shell. Initially it is bathed in uterine secretions that provide oxygen and metabolic substrates; however, these secretions soon become inadequate for support of further development. Therefore, within 24 hours of hatching (about day 6 after fertilization), the blastocyst implants in the uterine lining, which provides access to substrates (glycogen filled stromal cells) necessary for continued growth. Implantation involves movement of the blastocyst to an optimal location (typically the mid to upper anterior or posterior wall of the uterus), adhesion, and invasion. As the trophoblast erodes deeper into the decidua, vacuoles form and become confluent to form lacunae by day 13 after fertilization. The lacunar space eventually becomes the intervillous space.
The progenitor cytotrophoblast cell is the stem cell of the placenta. These cells proliferate throughout gestation, differentiating along two pathways to form either villous cytotrophoblast which ultimately can become syncytiotrophoblasts (outer cellular layer) or extravillous cytotrophoblasts (inner cellular layer) (algorithm 1). Syncytiotrophoblast is a specialized epithelium that has several functions, including transport of gases, nutrients, and waste products and synthesis of peptide and steroid hormones that regulate placental, fetal, and maternal systems. Extravillous trophoblast (EVT) has a proliferative component and an invasive component. There is also a migratory EVT, which is neither invasive nor proliferative. These cells populate the cell islands, septum, chorionic plate and chorion laeve.
At four to five weeks of gestation (menstrual dates), EVT erupts in columns with proliferative trophoblast at the base and invasive trophoblast at the distal portion of the column. Invasive EVT that invades decidua is called interstitial EVT, whereas EVT that invades and remodels the spiral arteries is called endovascular EVT. Endovascular invasion (intramural or intra-arterial) involves replacement or displacement of vascular smooth muscle and endothelial cells and transforms the narrow spiral arteries into wide uteroplacental arteries (algorithm 1). Anastomoses between the dilated spiral arteries and endometrial veins form maternal sinusoids, which eventually distribute blood into the low resistance vascular network of the lacunar system, thus establishing the uteroplacental circulation.
During invasion, EVT expresses specific proteins defining the stage and role in the differentiation and invasion process. These include integrin cell-extracellular matrix antigens, matrix metalloproteinases (MMPs), signal transduction proteins such as transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF) and VEGF receptors, and insulin-like growth factor 2 (IGF2).