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Planar cell polarity proteins, essential for cell organization, are understudied in the context of uterine physiology and implantation. PRICKLE proteins, components of PCP, are suggested to play critical roles in epithelial polarization and tissue morphogenesis. However, their function in the polarized unicellular layer of endometrial epithelium, which supports embryo implantation, is unknown. We developed an endometrial epithelial-specific knockout of mouse Prickle1 using Lactoferrin-iCre to investigate its role in uterine physiology. Prickle1 ablation in the endometrial epithelium of mice resulted in decreased embryo implantation by gestational day 4.5, leading to lower fertility. 3D imaging of the uterus revealed abnormal luminal folding, impaired luminal closure, and altered glandular length in mutant uteri. Additionally, we observed decreased aquaporin-2 expression, disrupted cellular architecture, and altered E-cadherin expression and localization in the mutant uterine epithelium. Evidence of epithelial\u2013mesenchymal transition was found within luminal epithelial cells, further linking PRICKLE1 loss to uterine pathologies. Furthermore, altered polarity of cell division leading to incomplete cytokinesis and increase in binuclear or multinucleated cells suggests a crucial role for PRICKLE1 in the maintenance of epithelial architecture. Our findings highlight PRICKLE1's critical role in the planar cell polarity pathway within the uterus, revealing its importance in the molecular and cellular responses essential for successful pregnancy and fertility.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgaf024","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T12:11:16Z","timestamp":1737720676000},"source":"Crossref","is-referenced-by-count":3,"title":["Loss of PRICKLE1 leads to abnormal endometrial epithelial architecture, decreased embryo implantation, and reduced fertility in mice"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6710-0530","authenticated-orcid":false,"given":"Emily R","family":"Roberts","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of Kansas Medical Center , Kansas City, KS 66160 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