Ligand-receptor signaling with endocannabinoids during peri-implantation events in mice, in the context of anandamide interacting with G-protein coupled receptors CB1 and CB2.
Endocannabinoids, a group of endogenously produced cannabinoid-like lipid molecules that activate G-protein coupled cannabinoid receptors, have been shown to play a critical role in various female reproductive events. There are two cannabinoid receptors: CB1, which is found in the testes and uterus, and CB2, which is found in the spleen and immune cells. More is understood about the role CB1 plays in the early stages of pregnancy than CB2. Embryos exposed to elevated levels of endocannabinoids or synthetic or natural cannabinoids show severe growth retardation, but can be rescued by the administration of a CB1, but not CB2, antagonist. Additionally, it appears that the absence of CB1 leads to oviductal retention of embryos, as does excessive exposure to THC. Endocannabinoid levels, primarily anandamide, are also tightly regulated during embryo implantation. Although the specifics of endocannabinoid signaling are not known, it appears a fine balance of endocannabinoid levels is needed to ensure successful pregnancy.