Mechanisms Regulating Immune Cell Contributions to Spiral Artery Modification – Facts and Hypotheses – A Review

Early during murine, human and porcine pregnancy, endometrium associated with developing placentae is enriched for uterine Natural Killer (uNK) cells. A shared role for uNK cells in each of these species is production of angiogenic growth factors. Many uNK cells are located in close proximity to or structurally integrated within the walls of endometrial vessels. In mice, uNK cells have been found essential for the initiation of pregnancy-associated spiral arterial modification through their production of interferon-γ. Unique aspects of uNK cell interactions with decidual endothelium are being defined using cell and tissue transfer into pregnant, alymphoid mice, adhesion of viable lymphocytes to frozen uterine tissue sections under shear forces, laser capture microdissection of uNK cells for quantitative RNA analyses and intravital microscopy. These studies indicate that uterine lymphocytes have a fundamental and major importance in promotion of angiogenesis within implantation sites that is regulated by the reproductive hormone cycle. Further, this work suggests that the pro-inflammatory endometrial cytokine response seen when peri-implantation conceptuses arrest has, as its target for destruction, newly developed endometrial vasculature rather than fetal trophoblast.