525. ROLES FOR HUMAN CHORIONIC GONADOTROPHIN IN EMBRYO-ENDOMETRIAL CROSS-TALK DURING BLASTOCYST IMPLANTATION

Abstract

Emerging evidence suggests an important role for the early embryo product human chorionic gonadotrophin (hCG) in embryo-endometrial interactions critical for successful embryo implantation¹. The human endometrium is also a source of hCG, with maximal expression of hCG and its receptor, hCG/LHR, in endometrial epithelial cells during the window of implantation in vivo^2,3, and in primary endometrial epithelial cells (EECs)³. Implantation is tightly regulated by growth and regulatory factors produced within the embryo-endometrial microenvironment. We hypothesise that embryo/endometrial-derived hCG mediates the molecular cross talk vital for successful implantation. The main objective of this study was to investigate the effect of hCG on the production of a selected cohort of 42 cytokines and growth factors by EECs. These included those with both known and previously unidentified roles during implantation. The secretory profile of cytokines/growth factors produced by EECs was also analysed. EECs (n=8 cultures) were isolated from biopsies collected from fertile cycling women. Cells were treated without or with recombinant hCG for 48 hr and conditioned media collected for quantitative analysis using Luminex^TM multiplex technology. For the first time, a secretory profile of 42 cytokines and growth factors produced by EECs was established, as was the identification of fibroblast growth factor-2 (FGF-2) secretion by human endometrial epithelium. hCG (2 IU/ml) significantly increased the production of a number factors including those with known roles during trophoblast migration and adhesion (CX3CL1; 71±31%, CXCL10; 67±24%, CCL4; 87±12%), in trophoblast differentiation (IL-1α ; 68±31%) and with unidentified roles during implantation (CCL22; 78±40%, GM-CSF; 45±16%, FGF-2; 50±25%; all p<0.05). Upregulation of the known hCG regulated proteins, VEGF and LIF, validated this study. These findings clearly support roles for the embryo/endometrium via hCG in actively contributing to the molecular cross-talk during the early stages of implantation.