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(MS29) GESTATION STAGE-DEPENDENT TROPHOBLAST CELL-NATURAL KILLER CELL INTERACTIONS. Soares, Michael1, Dai, Guoli1, Godwin, Alan1, Ain, Rupasri1, 1 University of Kansas Medical Center, Kansas City, Kansas, USA ABSTRACT- Rodents, as exemplified by the mouse and rat, have evolved highly efficient strategies for reproduction, some of which are homologous with strategies utilized by primates including the human. In this overview, we discuss interactions between trophoblast cells and natural killer (NK) cells situated at the maternal-fetal interface. We focus on a location where trophoblast cells and NK cells become associated with the maternal uterine vasculature; a region termed the uterine mesometrial compartment or metrial gland. The blood vessels at this site supply nutrients to the placenta and fetus and determine characteristics of their growth and development. Following implantation, NK cells expand in number and differentiate within the uterine mesometrial compartment. They come into contact with and modify uterine spiral arteries. These NK cell maturation processes are dependent upon the decidual milieu, including effective interleukin-11 and -15 signaling. During the last week of gestation, as uterine NK cells disappear, trophoblast cells exit the chorioallantoic placenta and move into locations previously occupied by NK cells; and further assist with nutrient delivery. The extent of trophoblast cell invasion is more pronounced in the rat than in the mouse. Invasive trophoblast cells possess a unique phenotype, which includes the production of hormones/cytokines belonging to the prolactin (PRL) family. NK cells and trophoblast cells communicate with each other through their synthesis and secretion of cytokines. These include interferon (IFN)-gamma, a NK cell product, and PRL-like protein-A (PLP-A), a trophoblast-derived hormone/cytokine. IFN-gamma antagonizes invasive trophoblast cells, while PLP-A inhibits NK cell cytokine production. Regulatory processes associated with the uterine mesometrial compartment can be investigated by exposing pregnant mice to hypoxia. Both NK cells and trophoblast cells are involved in successful adaptations to hypoxia. Collectively, NK cells and trophoblast cells participate in pregnancy-dependent physiological adjustments. Understanding the nature of trophoblast-NK cell interactions provides insights into regulatory processes occurring at the maternal-fetal interface. (Supported by NIH, HD20676, HD39878; Hall Family Foundation) KEY WORDS: trophoblast cells, placenta, natural killer cells, prolactin |
