{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:19:26Z","timestamp":1780679966509,"version":"3.54.1"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"6 October University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>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\/\u03b2-catenin and PI3K-AKT-mTOR signaling pathways, both essential for regulating endometrial receptivity and successful embryo implantation. Immunohistochemical testing showed a marked reduction in \u03b2-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\/\u03b2-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.<\/jats:p>","DOI":"10.1007\/s43032-025-01832-8","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T20:14:07Z","timestamp":1742415247000},"page":"1953-1958","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Disruption of the Wnt\/\u03b2-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"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4692-1998","authenticated-orcid":false,"given":"Zeyad Hossam Atta","family":"Khalil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Altayfa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"issue":"1","key":"1832_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.rbmo.2013.08.011","volume":"28","author":"C Coughlan","year":"2014","unstructured":"Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, Cutting R, Ong K, Sallam H, Li TC. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014;28(1):14\u201338. https:\/\/doi.org\/10.1016\/j.rbmo.2013.08.011.","journal-title":"Reprod Biomed Online"},{"issue":"12","key":"1832_CR2","doi-asserted-by":"publisher","first-page":"e1001356","DOI":"10.1371\/journal.pmed","volume":"9","author":"MN Mascarenhas","year":"2012","unstructured":"Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356. https:\/\/doi.org\/10.1371\/journal.pmed.","journal-title":"PLoS Med"},{"issue":"5","key":"1832_CR3","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.fertnstert.2012.03.010","volume":"97","author":"A Simon","year":"2012","unstructured":"Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril. 2012;97(5):1039\u201343. https:\/\/doi.org\/10.1016\/j.fertnstert.2012.03.010.","journal-title":"Fertil Steril"},{"issue":"1","key":"1832_CR4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/ijms21010023","volume":"21","author":"M Massimiani","year":"2019","unstructured":"Massimiani M, Lacconi V, La Civita F, Ticconi C, Rago R, Campagnolo L. Molecular signaling regulating Endometrium-Blastocyst crosstalk. Int J Mol Sci. 2019;21(1):23. https:\/\/doi.org\/10.3390\/ijms21010023.","journal-title":"Int J Mol Sci"},{"key":"1832_CR5","doi-asserted-by":"publisher","first-page":"110350","DOI":"10.1016\/j.cellsig.2022.110350","volume":"95","author":"S Daisy Precilla","year":"2022","unstructured":"Daisy Precilla S, Biswas I, Kuduvalli SS, Anitha TS. Crosstalk between PI3K\/AKT\/mTOR and WNT\/\u03b2-Catenin signaling in GBM - Could combination therapy checkmate the collusion? Cell Signal. 2022;95:110350. https:\/\/doi.org\/10.1016\/j.cellsig.2022.110350.","journal-title":"Cell Signal"},{"key":"1832_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.ebiom.2019.10.018","volume":"50","author":"Q Zhou","year":"2019","unstructured":"Zhou Q, Yan G, Ding L, Liu J, Yu X, Kong S, et al. EHD1 impairs decidualization by regulating the Wnt4\/\u03b2-catenin signaling pathway in recurrent implantation failure. EBioMedicine. 2019;50:343\u201354. https:\/\/doi.org\/10.1016\/j.ebiom.2019.10.018.","journal-title":"EBioMedicine"},{"key":"1832_CR7","doi-asserted-by":"publisher","first-page":"1061766","DOI":"10.3389\/fendo.2022.1061766","volume":"13","author":"J Ma","year":"2023","unstructured":"Ma J, Gao W, Li D. Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front Endocrinol (Lausanne). 2023;13:1061766. https:\/\/doi.org\/10.3389\/fendo.2022.1061766.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"1832_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15384047.2022.2108690","volume":"23","author":"CD Fleming-de-Moraes","year":"2022","unstructured":"Fleming-de-Moraes CD, Rocha MR, Tessmann JW, de Araujo WM, Morgado-Diaz JA. Crosstalk between PI3K\/Akt and Wnt\/\u03b2-catenin pathways promote colorectal cancer progression regardless of mutational status. Cancer Biol Ther. 2022;23(1):1\u201313. https:\/\/doi.org\/10.1080\/15384047.2022.2108690.","journal-title":"Cancer Biol Ther"}],"container-title":["Reproductive Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-025-01832-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43032-025-01832-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-025-01832-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T16:41:47Z","timestamp":1750783307000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43032-025-01832-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":8,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["1832"],"URL":"https:\/\/doi.org\/10.1007\/s43032-025-01832-8","relation":{},"ISSN":["1933-7191","1933-7205"],"issn-type":[{"value":"1933-7191","type":"print"},{"value":"1933-7205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"21 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the ethical standards of the institutional and national research committees, as well as the Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval was obtained from the Institutional Review Board (IRB) of October 6th University Hospital, with IRB approval number O6U-IRB-2024-058. Written informed consent was obtained from the patient before inclusion in the study, ensuring confidentiality and voluntary participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Informed consent was obtained from the patient to participate in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Informed consent was obtained from the patient for publication agreement of the paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. The patient has been informed that the information and images will be anonymized, ensuring that no identifying details will be disclosed. This consent process was conducted by ethical guidelines established by the Institution\u2019s Ethics Committee of October 6th University, ensuring the patient\u2019s autonomy, confidentiality, and rights were fully protected.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient Consent"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}