A novel technology for In Vitro and In Utero modification of Endometrial cells
Implantation failure is a major contributing factor to both the diagnosis of unexplained infertility and unsuccessful In Vitro Fertilisation (IVF) outcomes. Research efforts aimed at increasing IVF success rates have largely focussed on improving embryo quality and selection. The reciprocating partner in implantation, the endometrium, has received less attention or at least resulted in fewer useful advances. Difficulties in accessing the endometrium, coupled with the limited methods for bringing about alterations in this organ have left treatment options wanting. KODE™ modification is a proven technology used to impart functional changes to the cell surface by insertion of glycolipid-like constructs into the bilipid membrane of cells, altering antigen exhibition. This investigation set out to explore the ability of KODE™ constructs to modify endometrial epithelial cells (EECs) in order to impart functional changes in the attachment of trophoblastic spheroids in vitro and embryos in an in situ mouse model. Insertion and retention assays have demonstrated that the benign proof principle molecule, FSL A, successfully inserts into the target endometrial epithelial cells in an efficient manner. A decrease in spheroid attachment was unexpectedly demonstrated in an in vitro assay of FSL A-treated EEC monolayers (p< 0.001). Similarly, FSL B molecule also decreased the attachment potential in these cells. Results in vivo reflected those of in vitro assays, with decreased implantation rates observed when uterine endometrial cells were modified in situ by administration using a novel lavage technique. This is the first report that KODE™ technology can be used as a research tool to advance the understanding of cellular interactions in the uterine environment and the ultimate development of potential therapeutic applications for IVF.