Implantation and endometrial decidualization activate a unique population of maternal immune cells that iniltrate the uterus and play critical functions in trophoblast invasion, angiogenesis, spiral artery remodeling, and maternal tolerance to fetal alloantigens. Decidual natural killer cells (dNK) make up 70 percent of decidual leukocytes in the first trimester and are found in direct contact with trophoblasts. In contrast to natural killer cells in peripheral blood, these cells lack cytotoxic functions. They produce specific cytokines and angiogenic factors to regulate invasion of fetal trophoblasts and spiral artery remodeling (Hanna, 2006). hese and other unique properties distinguish dNK cells from circulating natural killer cells and from natural killer cells in the endometrium before pregnancy (Fu, 2013; Winger, 2013). dNK cells express both IL-8 and interferoninducible protein-1 0, which bind to receptors on invasive trophoblastic cells to promote their decidual invasion toward the spiral arteries. dNK cells also produce proangiogenic factors, including VEGF and placental growth factor (PIGF), which both promote vascular growth in the decidua.
FIGURE 5-1 1 Complete abortion specimens. A. Initially, the entire chorionic sac is covered with villi, and the embryo within is not visible B. With further growth, stretch and pressure prompt partial regression of the villi. Remaining villi form the future placenta, whereas the smooth portion is the chorion.
Trophoblasts also secrete speciic chemokines that attract the dNK cells to the maternl-fetal interface. hus, both cell types simultaneously attract each other. Decidual macro phages account for approximately 20 percent of leukocytes in the first trimester and elicit an M2-immunomodulatory phenotype (Williams, 2009). Remember, M1 macrophages are pro inflammatory, and M2 macrophages counter proinflammatory responses and promote tissue repair. In addition to a role in angiogenesis and spiral artery remodeling, dNK cells promote phagocytosis of cell debris (Faas, 2017). Concurrent with the critical role of maternal dNK cells and macro phages, T cell subsets aid tolerance toward the allogenic fetus. Regulatory T cells (Tregs) are essential for promoting immune tolerance. Other T cell subsets are present, such s Th 1, Th2 and Th 17, although their unctions are tightly regulated (Ruocco, 2014) .
Extravillous trophoblasts of the first-trimester placenta are highly invasive. his process occurs under low-oxygen conditions, and regulatory factors that are induced under hypoxic conditions are contributory (Soares, 2012). Invasive trophoblasts secrete numer vate proteinases already present in the decidua. Trophoblasts produce urokinase-type plasminogen activator, which converts plasminogen into the broadly acting serine protease, plasmin.
This in turn both degrades matrix proteins and activates M.1Ps.
One member of the MMP family, MMP-9, appears to be criti cal. The timing and extent of trophoblast invasion is regulated by a balanced interplay between pro-and anti invasive factors.
he relative ability to invade maternal tissue in early preg nancy compared with limited invasiveness in late pregnancy is ual factors. Trophoblasts secrete insulin-like growth factor II that promotes invasion into the decidua. Decidual cells secrete insulin-like growth factor binding-protein type 4, which blocks this autocrine loop.