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

Reproductive Biology and Endocrinology

James K Pru²  Jose M Teixeira¹  Lihua Zhang¹  Amanda L Patterson²  Ling Zhang¹ 

[1] Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 02114, USA;Department of Animal Sciences, Center for Reproductive Biology, Washington State University, Pullman, WA, 99164, USA

关键词: Uterus;    Progesterone;    Pregnancy;    Implantation;    Endometrium;    Decidualization;    Beta-catenin;   

Others  :  1150072
DOI  :  10.1186/1477-7827-10-75

 received in 2012-04-16, accepted in 2012-09-04,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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