New research indicates marijuana-like compounds called endocannabinoids alter genes and biological signals critical to the formation of a normal placenta during pregnancy and may contribute to pregnancy complications like preeclampsia.
The study offers new evidence that abnormal biological signaling by endocannabinoid lipid molecules produced by the body disrupts the movement of early embryonic cells important to a healthy pregnancy, in particular trophoblast cells that form the placenta. Abnormal placental function is common in preeclampsia – a medical condition of unknown cause that is a danger to mother and child.
The research – from scientists in the Division of Reproductive Sciences at Cincinnati Children’s Hospital Medical Center – analyzed mouse preimplantation embryos mutated to alter endocannabinoid signaling. They found that either silencing or enhancing endocannabinoid signaling adversely affects trophoblast stem cell migration.
“The findings or our investigation raise concerns that exposure to cannabis products may adversely affect early embryo development that is then perpetuated later in pregnancy,” said Sudhansu K. Dey, PhD., principal investigator on the study and division director. “Also, given that endocannabinoid signaling plays a key role in the central nervous system, it would be interesting in future studies to examine whether affected cell migration-related genes in early embryos also participate in neuronal cell migration during brain development.”
In one group of embryos endocannabinoid signaling was silenced by deleting the gene Cnr1, which activates endocannabinoid signaling processes. A second group of mice was mutated to produce elevated endocannabinoid levels similar to that observed in wild type mice treated with tetrahydrocannabinol (THC), the active psychotropic agent in cannabis. This was done by deleting the gene Faah, which breaks down molecules that activate endocannabinoid signaling.
In both groups, the expression of numerous genes known to be important to cell movement and embryo development was lower than in normal wild type mice. This included the development and migration of trophoblast stem cells. Trophoblast cells help anchor the conceptus with the uterus and also form much of the placenta, critical to establishment of maternal-fetal circulation and exchange of nutrients.
Researchers said mouse models developed for the current study (with silenced and elevated endocannabinoid signaling) may help advance more extensive studies on the causes of preeclampsia.