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First published online 3 July 2008
doi: 10.1242/dev.019810

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.019810v1 135/15/2659    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Laws, M. J. Articles by Bagchi, I. C. PubMed PubMed Citation Articles by Laws, M. J. Articles by Bagchi, I. C.

Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival

¹ Department of Veterinary Biosciences, and University of Illinois Urbana/Champaign, Urbana, IL 61802, USA.
² Department of Molecular and Integrative Physiology,
³ Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ New York University School of Medicine, NY 10016, USA.

^* Author for correspondence (e-mail: ibagchi{at}uiuc.edu)

Accepted 20 May 2008

In the uterus, the formation of new maternal blood vessels in the stromal compartment at the time of embryonic implantation is critical for the establishment and maintenance of pregnancy. Although uterine angiogenesis is known to be influenced by the steroid hormones estrogen (E) and progesterone (P), the underlying molecular pathways remain poorly understood. Here, we report that the expression of connexin 43 (Cx43), a major gap junction protein, is markedly enhanced in response to E in uterine stromal cells surrounding the implanted embryo during the early phases of pregnancy. Conditional deletion of the Cx43 gene in these stromal cells and the consequent disruption of their gap junctions led to a striking impairment in the development of new blood vessels within the stromal compartment, resulting in the arrest of embryo growth and early pregnancy loss. Further analysis of this phenotypical defect revealed that loss of Cx43 expression resulted in aberrant differentiation of uterine stromal cells and impaired production of several key angiogenic factors, including the vascular endothelial growth factor (Vegf). Ablation of CX43 expression in human endometrial stromal cells in vitro led to similar findings. Collectively, these results uncovered a unique link between steroid hormone-regulated cell-cell communication within the pregnant uterus and the development of an elaborate vascular network that supports embryonic growth. Our study presents the first evidence that Cx43-type gap junctions play a critical and conserved role in modulating stromal differentiation, and regulate the consequent production of crucial paracrine signals that control uterine neovascularization during implantation.

Key words: Implantation, Endometrium, Neovascularization, Estrogen, Connexin 43, Mouse

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Gap junctions: maternal role in implantation

Development 2008 135: e1502. [Full Text]  

This article has been cited by other articles:

				M. J. Laws, R. N. Taylor, N. Sidell, F. J. DeMayo, J. P. Lydon, D. E. Gutstein, M. K. Bagchi, and I. C. Bagchi Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival J. Cell Sci., August 1, 2008; 121(15): e1506 - e1506. [Full Text]