The balance of this network of signaling molecules is clearly inclined to pro-inflammation. In addition, choriodecidual leukocytes secreted chemokines and active MMP-9. Based on these findings, BTK signaling pathway inhibitor we propose that term choriodecidua contains a potential cellular source of pro-inflammatory mediators and the enzymatic machinery required for amniochorion extracellular matrix degradation associated with normal delivery at the end of gestation. Characterization of the specific subsets of cells participating in the secretion of these compounds is currently under way in our laboratory. These findings add functional meaning to old and new observations

describing the infiltration of leukocytes in reproductive tissues near the time of labor.[10, 14, 18, 27, 28, 30] Our group recently provided evidence supporting that the choriodecidua cellular composition is actively and selectively modified at gestational term with the arrival of specific lymphocyte subsets, Epigenetics Compound Library screening some of them expressing MMP-9, IL-1β, and TNF-α.[10, 17]Our findings using in vitro-cultured choriodecidual leukocytes are also complementary to the previously reported in vivo presence of leukocytes in the choriodecidua expressing pro-inflammatory mediators, such as those described in this

article, in human tissues experiencing labor.[10, 18, 31] Specific chemo-attraction and homing of leukocytes to term gestation choriodecidua have been pheromone proposed as the first step for conditioning a pro-inflammatory microenvironment resulting in the production of mediators for the induction

of labor at term pregnancy.[13, 32-34] Chemokines such as MIP-1α, MCP-1, IL-8, and RANTES are increased during labor in amniotic fluid, and this increase correlates with cervical dilation[33] and the number of leukocytes in reproductive tissues at term labor.[35-37] MIP-1α, IL-6, and MCP-1 are secreted by choriodecidual leukocytes,[8, 31] and these signals may attract and activate additional lymphocytes and monocytes, among other leukocytes.[34] According to the current hypothesis, once homing of leukocytes to the choriodecidua is under way, activation of the inflammatory cascade by a non-identified modulator will result in the massive local liberation of mediators, including IL-1β, TNF-α, and IL-6.[4, 5, 9, 12] Increased concentrations of these cytokines have been documented during labor in different compartments, including umbilical cord blood, amniotic fluid, and peripheral maternal blood.[3, 11, 16, 38] Choriodecidual cells may be a major source for these signals. These cytokines have been proposed as a first wave of signaling, acting on local cells and resulting in the production of a secondary wave of effector molecules.