Pregnancy success in mice requires appropriate cannabinoid receptor signaling for primary decidua formation
- Cincinnati Children's Research Foundation, United States
Abstract
With implantation mouse stromal cells begin to transform into epithelial-like cells surrounding the implantation chamber forming an avascular zone called the primary decidual zone (PDZ). In mouse, the PDZ forms a transient, size-dependent permeable barrier to protect the embryo from maternal circulating harmful agents. The process of decidualization is critical for early pregnancy maintenance in mice and humans. Mice deficient in cannabinoid receptors, CB1 and CB2, show compromised PDZ with dysregulated angiogenic factors, resulting in the retention of blood vessels and macrophages. This phenotype is replicated in Cnr1-/-, but not in Cnr2-/- mice. In vitro decidualization models suggest that Cnr1 levels substantially increase in mouse and human decidualizing stromal cells, and that neutralization of CB1 signaling suppresses decidualization and misregulates angiogenic factors. In sum, we propose that implantation quality depends on appropriate angiogenic events driven by the integration of CB2 in endothelial cells and CB1 in decidual cells.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute on Drug Abuse (DA006668)
- Sudhansu K Dey
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD068524)
- Sudhansu K Dey
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Pregnancy success in mice requires appropriate cannabinoid receptor signaling for primary decidua formation
eLife 9:e61762.
https://doi.org/10.7554/eLife.61762
