Khalil Zeyad Hossam Atta, Altayfa Omar
College of Medicine, Tanta University, Giza, Cairo, Egypt.
College of Medicine, October 6th University, 217G Pyramid Gardens, Giza, Cairo, Egypt.
Reprod Sci. 2025 Mar 19. doi: 10.1007/s43032-025-01832-8.
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.
一名34岁女性，有复发性植入失败（RIF）和不明原因不孕症的长期病史，前来进一步评估。分子分析显示，Wnt/β-连环蛋白和PI3K-AKT-mTOR信号通路之间的串扰存在显著破坏，这两条信号通路对于调节子宫内膜容受性和胚胎成功植入都至关重要。免疫组织化学检测显示，β-连环蛋白核转位显著减少，AKT磷酸化降低65%，导致细胞增殖和分化等细胞过程受损。这种破坏导致子宫内膜蜕膜化不完全，这在她反复植入失败中起了核心作用。包括激素治疗和体外受精（IVF）在内的传统生育治疗均无效。因此，我们探索了旨在恢复这些信号通路功能以增强子宫内膜容受性的靶向分子疗法。该病例强调了Wnt/β-连环蛋白和PI3K-AKT-mTOR通路在子宫内膜功能中的关键作用，并突出了通过解决特定分子缺陷来治疗RIF的新型治疗策略的潜力。
