This project aims to elucidate how Herpes Simplex Virus type 1 (HSV-1) infection disrupts endometrial epithelial integrity and impairs endometrial receptivity, using patient-derived organoids (PDOs) as an advanced translational model. PDOs will be generated from endometrial biopsies obtained from four patients undergoing hysteroscopy and cultured in a Matrigel- based three-dimensional system. Once established, the organoids will be characterized by the expression of epithelial markers: CK7 and E-cadherin. They will then be infected with HSV-1 to evaluate viral replication kinetics at 24 and 48 hours post-infection, using digital droplet PCR and immunocytochemistry. The effect of infection on epithelial barrier integrity will be assessed by analyzing tight and adherens junction proteins (TJP1-3, Claudins, E-cadherin) and MMP3 expression using RT-PCR, Western blotting, and immunofluorescence. Morphological and ultrastructural alterations, including changes in microvilli and nuclear morphology, will be examined through confocal and electron microscopy. In parallel, cytokine profiling (IL-1β,TNF-α) by Multiplex ELISA will provide insights into the inflammatory responses associated with epithelial disruption. Finally, markers of endometrial receptivity—such as integrin αVβ3, MUC1, LIF, SPP1, PAEP, HOXA10, HOXA11, and hormone receptors—will be analyzed to determine how HSV-1 infection affects the molecular pathways essential for embryo implantation. Overall, this project will provide novel insights into the mechanisms through which HSV-1 compromises endometrial health, highlighting the molecular events leading to loss of epithelial integrity and altered receptivity. These findings may contribute to understanding implantation failure and adverse pregnancy outcomes associated with viral infections.