532. SOLUBLE MEDIATORS IN THE HUMAN UTERINE CAVITY: POTENTIAL ROLES IN EMBRYO IMPLANTATION

Abstract

Embryo implantation requires synchronized dialogue between a receptive endometrium and an activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle there is increased glandular secretion into the uterine lumen. These secretions likely contain important mediators that modulate the endometrium and support the conceptus during implantation. Previously we identified that several chemokines were maximally produced during the MS phase by endometrial glandular epithelium (GE) (1, 2) and the presence of chemokine receptors on GE and human trophoblast (3). Furthermore recombinant human chemokines and endometrial epithelial cell-conditioned media stimulated trophoblast migration; this was attenuated by neutralizing specific chemokines (3). Chemokines also regulate a variety of adhesion and ECM molecules on trophoblast (4). Thus chemokines have important roles during embryo implantation. We hypothesized that chemokines are secreted into the uterine cavity and may act on the implanting blastocyst and the endometrium. This study aimed to identify chemokines in uterine fluid (collected by flushing the uterine cavity with 5mls of saline) from fertile women during the proliferative (non-receptive; n=4) and MS (receptive; n=4) phases of the cycle, and from women with unexplained infertility during the MS phase (n=4). Uterine fluid was analyzed using quantitative Milliplex^TM Luminex® 42-plex cytokine/chemokine assays revealing the presence of IL-8, CCL2, CCL4, CCL7, CCL11, CCL22 and CX3CL1 in uterine fluid from all women. Importantly chemokine profiles were altered with both cycle phase and fertility; for example CCL4 and CCL22 levels were lower in the infertile cohort, where as CCL2 levels were higher in uterine fluid collected during the proliferative phase. Identifying the soluble mediators in human uterine fluid may provide potential markers of endometrial receptivity, insight into the unique microenvironment essential for pregnancy and a profile of maternal factors that influence the implanting blastocyst.