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 vivo2,3, 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 LuminexTM 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.