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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Cell Transdifferentiation, Decidua, Endometrium, Epithelial Cells, Epithelial-Mesenchymal Transition, Estrogens, Estrous Cycle, Female, Mice, Mice, Inbred ICR, Mice, Mutant Strains, Mice, Transgenic, Myometrium, Placentation, Pregnancy, Progesterone, Pseudopregnancy, Random Allocation, Signal Transduction, Stromal Cells, beta Catenin.
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Is endometrial stromal beta-catenin required for steroid-dependent mesenchymal-epithelial cross talk and decidualization? Context: Beta-catenin is part of a protein complex associated with adherens junctions. When allowed to accumulate to sufficient levels in its dephosphorylated form, beta-catenin serves as a transcriptional co-activator associated with a number of signaling pathways, including steroid hormone signaling pathways. To investigate the role of beta-catenin in progesterone (P₄) signaling and female reproductive physiology, conditional ablation of Ctnnb1 from the endometrial mesenchymal (i.e. stromal and myometrial), but not epithelial, compartment was accomplished using the Amhr2-Cre mice. Experiments were conducted to assess the ability of mutant female mice to undergo pregnancy and pseudopregnancy by or through oil-induced decidualization. The ability of uteri from mutant female mice to respond to estrogen (E₂) and P₄ was also determined. Conditional deletion of Ctnnb1 from the mesenchymal compartment of the uterus resulted in infertility stemming, in part, from complete failure of the uterus to decidualize. E₂-stimulated epithelial cell mitosis and edematization were not altered in mutant uteri indicating that the mesenchyme is capable of responding to E₂. However, exposure of ovariectomized mutant female mice to a combined E₂ and P₄ hormone regimen consistent with early pregnancy revealed that mesenchymal beta-catenin is essential for indirectly opposing E₂-induced epithelial proliferation by P₄ and in some mice resulted in development of endometrial metaplasia. Lastly, beta-catenin is also required for the induced expression of genes that are known to play a fundamental role in decidualization such as Ihh, Ptch1, Gli1 and Muc1
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Three salient points derive from these studies. First, the findings demonstrate a mechanistic linkage between the P₄ and beta-catenin signaling pathways. Second, they highlight an under appreciated role for the mesenchymal compartment in indirectly mediating P₄ signaling to the epithelium, a process that intimately involves mesenchymal beta-catenin. Third, the technical feasibility of deleting genes in the mesenchymal compartment of the uterus in an effort to understand decidualization and post-natal interactions with the overlying epithelium has been demonstrated. It is concluded that beta-catenin plays an integral role in selective P₄-directed epithelial-mesenchymal communication in both the estrous cycling and gravid uterus. Final Decision: yes