Experts in the Division of Reproductive Scientists at Cincinnati Children's Hospital Medical Center have shown new evidence in The Journal of Biological Chemistry, that the movement of early embryonic cells, which are critical to a healthy pregnancy, in particular trophoblast cells that form the placenta, are disrupted by abnormal biological signaling by endocannabinoid lipid molecules that are produced by the body.
This study supports prior research from August of this year in Drug Testing and Analysis, which indicated that the THC (tetrahydrocannabinol) contained in 'high potency' marijuana and other brands of 'synthetic marijuana', may damage embryonic development, as early as two weeks after conception.
Preeclamspia is a medical condition during pregnancy in which the mother develops high blood pressure and has a significant amount of protein in the urine. It is dangerous for both mother and child; abnormal placental function is common with this condition. Previous research had yet to identify any causes.
After analyzing mouse preimplantation embryos that were mutated to change endocannabinoid signaling, the team found that trophoblast stem cell migration undermines either silencing or enhancing endocannabinoid signaling.
Sudhansu K. Dey, Ph.D., division director and co-leading author with Huirong Xie and Xiaofei Sun, revealed:
"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. 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."
Prior studies by Dey's laboratory showed that in order to have a healthy pregnancy and birth, the timing of critical events in early pregnancy, such as when and how well an embryo implants in the uterus, is key.
One of his studies in 2006 showed that smoking marijuana early in pregnancy and even at the time of conception prevents embryos' safe passage from the ovary to the uterus, resulting in early pregnancy failure.
The current study was set to examine embryos that were not yet implanted inside a woman's uterus. In order to see how the expression levels of genes crucial to healthy embryo development were affected in embryos with abnormal endocannabinoid signaling, the team conducted DNA microarray analyses.
Endocannabinoid signaling was silenced in one group of embryos by deleting the gene Cnr1, which activates endocannabinoid signaling processes.
A different group of mice was mutated to create similar levels much like those observed in wild type mice treated with THC, the active psychotropic agent in cannabis. The gene Faah, which breaks down molecules that activate endocannabinoid signaling, had to be cut out for this to be done.
After examining the two groups, the expression of several genes vital in embryo development and cell movement was found to be lower than in normal wild type mice. This included trophoblast stem cells' growth and migration. Trophoblast cells help hold the embryo with the uterus while forming much of the placenta, which connects the fetus to the uterine wall allowing for the exchange of nutrients.
Extensive research conducted in the future on the causes of preeclampsia will be advanced by using the mouse models that were created in this study, the authors said.
Written by Sarah Glynn