Background: Endometrial receptivity is critical for successful reproduction. The endometrium must be receptive and the blastocyst hatched and appropriately developed to allow adhesion and subsequent implantation. Assisted reproductive technologies have optimised the production of quality embryos. However, success rates have not changed significantly; ANZARD data indicates no change in the live birth rate from 2010 – 2015 (18.1%). These data indicate a need to gain greater understanding of, and the factors involved in endometrial receptivity to provide targets for improving reproductive outcomes.
Aim: Determine and validate a proteomic signature of human endometrial epithelial receptivity and assess the functional role of these proteins.
Methods: Hormonally primed (estrogen/progesterone) primary human endometrial epithelial cells (HEEC) were co-cultured with spheroids of human trophoblast stem cells (TS) to mimic blastocyst adhesion to the endometrium. HEEC monolayers were designated “adhesive” or “non-adhesive” based on assessment of TS adhesion after 6-hours co-culture. Matched hormonally primed HEEC monolayer-only cultures were designated ‘receptive’ or ‘non-receptive’ based on TS adhesion and subjected to proteomic comparison to provide a signature of receptivity, the epithelial “receptome”. GO analysis determined functional processes regulated by these proteins. Immunohistochemistry validated proteins in ‘receptive’ (mid-secretory phase) versus ‘non-receptive’ (proliferative phase) human endometrium.
Results: 136 proteins were upregulated and 132 downregulated in the human epithelial receptome. Highly upregulated proteins include CDA, ACOT1, MAGT1, STMN1, PC4, and KYNU. CDA and STMN1 have previously been identified in the receptive endometrium, confirming the validity of this model. Cellular protein complex disassembly, translation, neutrophil degranulation and associated immune processes were enriched in the upregulated receptome proteins. CDA and ACOT1 have been validated as localized and elevated in the receptive human endometrium.
Conclusion: A proteomic signature of human endometrial epithelial receptivity has been determined and validated in the human endometrium.