Mice Missing Cnr1 and Cnr2 Show Implantation Defects
Overview
Affiliations
Cannabinoid/endocannabinoid signaling is primarily mediated by cannabinoid receptor type 1 (CB1; encoded by Cnr1) and/or type 2 (CB2; encoded by Cnr2). Here, we show that Cnr1-/-Cnr2-/- mice are subfertile as a result of compromised implantation. Upon implantation, the epithelium is smooth and adhered to the blastocyst trophectoderm within the implantation chamber (crypt) in wild-type mice, whereas the epithelium in Cnr1-/-Cnr2-/- mice is ruffled, which compromises appropriate blastocyst-uterine interactions. The suboptimal implantation leads to higher incidence of pregnancy failure in Cnr1-/-Cnr2-/- mice. Histological analysis revealed heightened edema around the implantation chamber in these deleted females. With the use of a reporter mouse line, we observed that CB2 is present on endothelial cells of uterine blood vessels, and its absence leads to blood vessel leakage during implantation. These results suggest that appropriately regulated uterine edema is important to optimal implantation.
Saini B, Kumar A, Ahmad S, Mehrotra A, Sachan S, Singh R Mol Biol Rep. 2025; 52(1):167.
PMID: 39873827 DOI: 10.1007/s11033-025-10233-8.
Aikawa S, Matsuo M, Akaeda S, Sugimoto Y, Arita M, Isobe Y JCI Insight. 2024; 9(19).
PMID: 39377223 PMC: 11466189. DOI: 10.1172/jci.insight.181865.
Endocannabinoids and their receptors modulate endometriosis pathogenesis and immune response.
Lingegowda H, Zutautas K, Wei Y, Yolmo P, Sisnett D, McCallion A Elife. 2024; 13.
PMID: 39120997 PMC: 11315450. DOI: 10.7554/eLife.96523.
Roles of lipid mediators in early pregnancy events.
Aikawa S, Hirota Y Reprod Med Biol. 2024; 23(1):e12597.
PMID: 39010880 PMC: 11247399. DOI: 10.1002/rmb2.12597.
Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy.
Rava A, Trezza V Int J Mol Sci. 2023; 24(6).
PMID: 36982295 PMC: 10048990. DOI: 10.3390/ijms24065220.