Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization
<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 numbe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-09-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | http://www.rbej.com/content/10/1/75 |
| _version_ | 1818141482406641664 |
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| author | Zhang Ling Patterson Amanda L Zhang Lihua Teixeira Jose M Pru James K |
| author_facet | Zhang Ling Patterson Amanda L Zhang Lihua Teixeira Jose M Pru James K |
| author_sort | Zhang Ling |
| collection | DOAJ |
| description | <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 (P<sub>4</sub>) 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 (E<sub>2</sub>) and P<sub>4</sub> 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. E<sub>2</sub>-stimulated epithelial cell mitosis and edematization were not altered in mutant uteri indicating that the mesenchyme is capable of responding to E<sub>2</sub>. However, exposure of ovariectomized mutant female mice to a combined E<sub>2</sub> and P<sub>4</sub> hormone regimen consistent with early pregnancy revealed that mesenchymal beta-catenin is essential for indirectly opposing E<sub>2</sub>-induced epithelial proliferation by P<sub>4</sub> 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 P<sub>4</sub> and beta-catenin signaling pathways. Second, they highlight an under appreciated role for the mesenchymal compartment in indirectly mediating P<sub>4</sub> 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 P<sub>4</sub>-directed epithelial-mesenchymal communication in both the estrous cycling and gravid uterus.</p> |
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| institution | Directory Open Access Journal |
| issn | 1477-7827 |
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| last_indexed | 2024-12-11T11:00:35Z |
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| spelling | doaj.art-3e1ef24f03b14c2ba71460f72c1aa05e2022-12-22T01:09:53ZengBMCReproductive Biology and Endocrinology1477-78272012-09-011017510.1186/1477-7827-10-75Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualizationZhang LingPatterson Amanda LZhang LihuaTeixeira Jose MPru James K<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 (P<sub>4</sub>) 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 (E<sub>2</sub>) and P<sub>4</sub> 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. E<sub>2</sub>-stimulated epithelial cell mitosis and edematization were not altered in mutant uteri indicating that the mesenchyme is capable of responding to E<sub>2</sub>. However, exposure of ovariectomized mutant female mice to a combined E<sub>2</sub> and P<sub>4</sub> hormone regimen consistent with early pregnancy revealed that mesenchymal beta-catenin is essential for indirectly opposing E<sub>2</sub>-induced epithelial proliferation by P<sub>4</sub> 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 P<sub>4</sub> and beta-catenin signaling pathways. Second, they highlight an under appreciated role for the mesenchymal compartment in indirectly mediating P<sub>4</sub> 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 P<sub>4</sub>-directed epithelial-mesenchymal communication in both the estrous cycling and gravid uterus.</p>http://www.rbej.com/content/10/1/75Beta-cateninDecidualizationEndometriumImplantationPregnancyProgesteroneUterus |
| spellingShingle | Zhang Ling Patterson Amanda L Zhang Lihua Teixeira Jose M Pru James K Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization Reproductive Biology and Endocrinology Beta-catenin Decidualization Endometrium Implantation Pregnancy Progesterone Uterus |
| title | Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization |
| title_full | Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization |
| title_fullStr | Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization |
| title_full_unstemmed | Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization |
| title_short | Endometrial stromal beta-catenin is required for steroid-dependent mesenchymal-epithelial cross talk and decidualization |
| title_sort | endometrial stromal beta catenin is required for steroid dependent mesenchymal epithelial cross talk and decidualization |
| topic | Beta-catenin Decidualization Endometrium Implantation Pregnancy Progesterone Uterus |
| url | http://www.rbej.com/content/10/1/75 |
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