Journal
DEVELOPMENT
Volume 135, Issue 15, Pages 2659-2668Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.019810
Keywords
implantation; endometrium; neovascularization; estrogen; connexin 43; mouse
Categories
Funding
- NCRR NIH HHS [C06 RR 16515-01, C06 RR016515] Funding Source: Medline
- NICHD NIH HHS [R01 HD 43381, R01 HD 55379, R01 HD 33238, R01 HD055379-01A1, U54 HD 055787, R01 HD055379, R01 HD044611, R01 HD 44611, R01 HD043381-05, R01 HD043381, U54 HD055787, U54 HD055787-01A10003] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available