Disruption of the Wnt/β-Catenin and PI3K-AKT-mTOR Crosstalk in Endometrial Stromal Cells: A Case Report of Impaired Decidualization Leading to Recurrent Implantation Failure and Potential Pathway-Specific Therapeutic Interventions
Zain Khalil, Omar Altayfa
Abstract
A 34-year-old woman with a long-standing history of recurrent implantation failure (RIF) and unexplained infertility presented for further evaluation. Molecular analysis revealed a significant disruption in the crosstalk between the Wnt/β-catenin and PI3K-AKT-mTOR signaling pathways, both essential for regulating endometrial receptivity and successful embryo implantation. Immunohistochemical testing showed a marked reduction in β-catenin nuclear translocation and a 65% decrease in AKT phosphorylation, leading to impaired cellular processes such as proliferation and differentiation. This disruption contributed to incomplete decidualization of the endometrium, which played a central role in her repeated implantation failures. Conventional fertility treatments, including hormone therapy and in vitro fertilization (IVF), were ineffective. Consequently, we explored targeted molecular therapies aimed at restoring functionality within these signaling pathways to enhance endometrial receptivity. This case underscores the critical role of the Wnt/β-catenin and PI3K-AKT-mTOR pathways in endometrial function and highlights the potential for novel therapeutic strategies in treating RIF by addressing specific molecular defects.