Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization

• Main Authors: Zhang Ling (Author), Patterson Amanda L (Author), Zhang Lihua (Author), Teixeira Jose M (Author), Pru James K (Author)
• Format: Book
• Published: BMC, 2012-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1477-7827-10-75; 1477-7827
• Keywords: Beta-catenin; Decidualization; Endometrium; Implantation; Pregnancy; Progesterone; Uterus; Gynecology and obstetrics; RG1-991; Reproduction; QH471-489
• Source: Reproductive Biology and Endocrinology, Vol 10, Iss 1, p 75 (2012)

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>To investigate the role of beta-catenin in progesterone (P₄) signaling and female reproductive physiology, conditional ablation of <it>Ctnnb1</it> from the endometrial mesenchymal (<it>i.e.</it> stromal and myometrial), but not epithelial, compartment was accomplished using the <it>Amhr2-Cre</it> 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.</p> <p>Results</p> <p>Conditional deletion of <it>Ctnnb1</it> 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 <it>Ihh</it>, <it>Ptch1</it>, <it>Gli1</it> and <it>Muc1</it></p> <p>Conclusions</p> <p>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.</p>