Molecular crosstalk at the endometrium-embryo interface

Abstract

Embryo implantation relies on tightly regulated molecular interactions between the endometrium and the developing embryo, however the relative contributions of each remain poorly understood. The main objective of this Master Thesis is to understand the molecular and genomic crosstalk between endometrium and embryo during implantation using a human in vitro model consisting of endometrial organoids derived from healthy fertile women and blastoids (embryo-like structures). To unravel the maternal and embryonic contributions, bulk RNA sequencing was integrated with genotyping, and a workflow was developed to assign the origin of expressed variants. Differential expression analysis identified 264 upregulated and 172 downregulated genes associated with blastoid attachment under hormonally induced conditions. Integration of variant profiles enabled classification of the assignment of gene expression to maternal, embryonic, or shared origin, revealing key pathways related to immune response, cell adhesion, and extracellular matrix remodeling. Consistently origin-assigned genes across donor-derived models were identified from implantation-related interactions. These findings demonstrate that integration of genomic data enhances the resolution of embryo-endometrium crosstalk and provides novel insights into mechanisms underlying implantation success and failure.