biostudies-literatureUnknown27(3)Zhou XNational Natural Science Foundation of ChinaPoor endometrial receptivity results in embryo implantation failure. Acquisition of endometrial receptivity involves substantial structural alterations in the cytoskeleton and plasma membrane of epithelial cells, which facilitate embryo adhesion. However, the underlying molecular mechanism remains largely unknown. In this study, we identified that α-actinin-1 (ACTN1) was significantly downregulated in the mid-secretory phase of the endometrium compared with other phases; however, ACTN1 significantly increased in women with recurrent implantation failure (RIF). In Ishikawa and human endometrial epithelial cells (HEECs), ACTN1 overexpression significantly decreased NEBL levels, enhanced F-actin fiber levels, and caused a notable impairment in blastocyst adhesion, which mimicked the process oiScience109046https://www.ebi.ac.uk/biostudies/studies/S-EPMC10879697biostudies-literatureUpregulated α-actinin-1 impairs endometrial epithelial cell adhesion by downregulating NEBL in recurrent implantation failure.PMC10879697Duan JChen QZhou WZhou XZhang AfalseUpregulated α-actinin-1 impairs endometrial epithelial cell adhesion by downregulating NEBL in recurrent implantation failure.Poor endometrial receptivity results in embryo implantation failure. Acquisition of endometrial receptivity involves substantial structural alterations in the cytoskeleton and plasma membrane of epithelial cells, which facilitate embryo adhesion. However, the underlying molecular mechanism remains largely unknown. In this study, we identified that α-actinin-1 (ACTN1) was significantly downregulated in the mid-secretory phase of the endometrium compared with other phases; however, ACTN1 significantly increased in women with recurrent implantation failure (RIF). In Ishikawa and human endometrial epithelial cells (HEECs), ACTN1 overexpression significantly decreased NEBL levels, enhanced F-actin fiber levels, and caused a notable impairment in blastocyst adhesion, which mimicked the process o2024-01-01T00:00:00Z2024 Mar2026-07-14T16:27:55.835Z2025-04-06T12:30:20.317ZS-EPMC108796973838484810.1016/j.isci.2024.109046