Cdh1 Is Essential for Endometrial Differentiation, Gland Development, and Adult Function in the Mouse Uterus1
Open Access
- 1 May 2012
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 86 (5), 141-10
- https://doi.org/10.1095/biolreprod.112.098871
Abstract
CDH1 is a cell-cell adhesion molecule expressed in the epithelium to coordinate key morphogenetic processes, establish cell polarity, and regulate epithelial differentiation and proliferation. To determine the role of CDH1 in the mouse uterus, Cdh1 was conditionally ablated by crossing Pgr-Cre and Cdh1-flox mice, and the phenotype was characterized. We found that loss of Cdh1 results in a disorganized cellular structure of the epithelium and ablation of endometrial glands in the neonatal uterus. Cdh1d/d mice lost adherens junctions (CTNNB1 and CTNNA1) and tight junctions (claudin, occludin, and ZO-1 proteins) in the neonatal uterus, leading to loss of epithelial cell-cell interaction. Ablation of Cdh1 induced abnormal epithelial proliferation and massive apoptosis, and disrupted Wnt and Hox gene expression in the neonatal uterus. Although the uteri of Cdh1d/d mice did not show any myometrial defects, ablation of Cdh1 inhibited expression of epithelial (cytokeratin 8) and stromal (CD10) markers. Cdh1d/d mice were infertile because of defects during implantation and decidualization. Furthermore, we showed in the model of conditional ablation of both Cdh1 and Trp53 in the uterus that interrupting cell cycle regulation through the loss of Cdh1 leads to abnormal uterine development. The uteri of Cdh1d/d Trp53d/d mice exhibited histological features of endometrial carcinomas with myometrial invasion. Collectively, these findings suggest that CDH1 has an important role in structural and functional development of the uterus as well as adult uterine function. CDH1 has a capacity to control cell fate by altering directional cell proliferation and apoptosis.Keywords
This publication has 49 references indexed in Scilit:
- Brief Exposure to Progesterone During a Critical Neonatal Window Prevents Uterine Gland Formation in Mice1Biology of Reproduction, 2012
- Postnatal Deletion of Wnt7a Inhibits Uterine Gland Morphogenesis and Compromises Adult Fertility in Mice1Biology of Reproduction, 2011
- p53, Stem Cells, and Reprogramming: Tumor Suppression beyond Guarding the GenomeGenes & Cancer, 2011
- WNTs in the Neonatal Mouse Uterus: Potential Regulation of Endometrial Gland DevelopmentBiology of Reproduction, 2010
- Foxa2 Is Essential for Mouse Endometrial Gland Development and Fertility1Biology of Reproduction, 2010
- Constitutive Activation of Smoothened Leads to Female Infertility and Altered Uterine Differentiation in the Mouse1Biology of Reproduction, 2010
- Molecular Profiling of Endometrial MalignanciesObstetrics and Gynecology International, 2010
- Cadherin-mediated Intercellular Adhesion and Signaling Cascades Involving Small GTPasesCold Spring Harbor Perspectives in Biology, 2009
- Diverse roles of E‐cadherin in the morphogenesis of the submandibular gland: Insights into the formation of acinar and ductal structuresDevelopmental Dynamics, 2008
- Conditional Loss of Uterine Pten Unfailingly and Rapidly Induces Endometrial Cancer in MiceCancer Research, 2008