Decidual Natural Killer Cells: Key Regulators of Placental Development (a Review)

Establishment of pregnancy initiates a dynamic and predictable series of changes in the uterus. In rodents, the trophectoderm of the blastocyst develops through the stage of an ectoplacental cone to become the placenta. The inner cell mass becomes the fetus and its associated extra-embryonic ectoderm and mesoderm. Maternal changes support development of the conceptus. These begin in the uterine stroma, which undergoes a process known as decidualization, and progress to include dilation and elongation of the uteroplacental arteries and activation and proliferation of specialized large granulated lymphocytes in the decidua basalis. This review focuses on these pregnancy-associated lymphocytes, known as uterine Natural Killer (uNK) cells and on their interactions with the other tissues that form the mesometrial aspect of the mouse maternal-fetal interface. Analogous lymphocytes are present in the decidualized human uterus. Understanding of uNK cell biology has advanced significantly through histological studies of implantation sites in immune deficient mice. Here, we summarize the key studies in lymphocyte-, cytokine- and cytokine receptor-deficient mice and in four enhanced models of gestation in these mice that incorporate transplantation or therapy with biologically active molecules.