(W1289) ESTABLISHMENT OF IMPLANTATION MODEL WITH HUMAN EXPANDED POTENTIAL STEM CELL DERIVED EMBRYO SURROGATE AND OPEN-FACED ENDOMETRIAL LAYER FOR STUDYING IMPLANTATION IN IVF PATIENTS
Abstract: Successful pregnancy requires the implantation of a competent blastocyst in receptive endometrium. Despite the use of in vitro fertilization (IVF), many women still fail to conceive due to endometrial or embryo problems. Studying embryo implantation in vivo is limited by ethical concerns. This study aimed to develop an implantation model with embryo surrogate and an expandable endometrial cell culture system for the study on implantation processes. Our team has generated a trophoblastic spheroid (BAP-EB) derived from human expanded potential stem cells (hEPSC-em) as human embryo surrogate. hEPSC-em-BAP-EB differentiated for 48h (hEPSC-em-BAP-EB-48h) are early trophectoderm (TE) like and less adhesive on the receptive Ishikawa cell, but after they are differentiated for 72h (hEPSC-em-BAP-EB-72h), they are polar TE like and can strongly attached onto receptive endometrial cell line. Endometrial organoids followed by open-faced endometrial layers (OFELs) culture were established using samples from IVF patients. It was found that endometrial organoids preserved the phenotypical and functional properties of endometrial glands. OFELs cultured in three different conditions were found to be hormone responsive. While hormone treatment had no effect on endometrial receptivity markers, it induced early epithelial to mesenchymal transition in OFEL. An attachment assay by coculturing OFEL with hEPSC-em-BAP-EB-72h was established. Critically, the attachment rate of hEPSC-em-BAP-EB on hormone treated OFEL was significantly higher than the non-treated OFEL. In conclusion, receptive OFELs were successfully established from endometrial organoids derived from IVF patients, and the coculture model with hEPSC-em-BAP-EB represented the first step toward the establishment of a 3D endometrium model that better mimics the implantation process.
Funding Source: This work was partly supported by Health and Medical Research Fund (grant numbers: HMRF #11222296) from the Food and Health Bureau, Government of the Hong Kong Special Administrative Region.
