title: Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Patterson
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhang
authors.forename: Jose M
authors.initials: JM
authors.lastname: Teixeira
authors.forename: James K
authors.initials: JK
authors.lastname: Pru
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D003656:Decidua / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009215:Myometrium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010929:Placentation; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D011555:Pseudopregnancy / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D004967:Estrogens; D051176:beta Catenin; D011374:Progesterone