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Background: At the time of implantation, the blastocyst produces a significant amount of lactic acid (LA), creating a microenvironment characterized by high lactate and low pH. Historically considered a ‘by-product’ of metabolism, studies have revealed lactate to be a key regulator of cell function, with a lactate-specific receptor, GPR81, recently identified. Further, lactate is an important signalling molecule in cancers promoting ECM breakdown, angiogenesis and immunosuppression, processes vital for successful implantation. Hence, LA could be an early embryonic signal to facilitate endometrial remodelling for receptivity and implantation. Aim: To determine the role of blastocyst-derived lactate on cellular functions/remodelling and transcriptional changes essential for endometrial receptivity and successful implantation. Methods: To assess functional changes to the endometrium, hormonally primed ECC-1 and Ishikawa cells were exposed to LA, LA + neutralized pH (nLA) or acidic pH (pHL), before analysis of tight junction integrity (TER), cellular proliferation and changes to gene expression. LA’s effects on endometrial stromal cell decidualization and migratory capacity, as well as HUVEC endothelial tube formation/angiogenesis, were also determined. Results: Cellular TER and proliferation were significantly downregulated in ECC-1 cells exposed to 2.5, 5 and 7.5mM LA ( P<0.01), while exposure to nLA or pHL alone had no effect. Upregulation of GLUT4, GPR81, VEGF, SNAI1, and RELA mRNA expression was observed following exposure of Ishikawa cells to combined LA + pHL(P<0.05), while MCT-1 expression decreased. Additionally, 5mM LA increased the migratory capacity of decidualized stromal cells (P<0.05) without changing the extent of decidualization. HUVEC tube formation was significantly increased by 5mM LA exposure ( P<0.01). Conclusion: The specialized microenvironment created by the blastocyst, of both high lactate and low pH, enhances endometrial remodelling for receptivity and implantation through functional changes to epithelial, stromal and endothelial cells in the endometrium. Therefore, LA appears to be an important signalling molecule in the maternal-fetal dialogue underpinning implantation.