Researchers from Western University and Queen’s University report that regular exposure to THC, the main psychoactive ingredient in cannabis, during pregnancy has significant impact on placental and fetal development. With more than a year since the legalization of recreational cannabis in Canada, the effects of its use during pregnancy are only now beginning to be understood, according to the scientists.
The study (“Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta”), published in Scientific Reports, uses a rat model and human placental cells to show that maternal exposure to THC during pregnancy has a measurable impact on both the development of the organs of the fetus and the gene expression that is essential to placental function. The researchers demonstrated in a rat model that regular exposure to a low-dose of THC that mimics daily use of cannabis during pregnancy led to a reduction in birth weight of 8% and decreased brain and liver growth by more than 20%.
“One in five women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9–tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC (3 mg/kg) from embryonic (E)6.5 through 22. Dams were allowed to deliver normally to measure pregnancy and neonatal outcomes, with a subset sacrificed at E19.5 for placenta assessment via immunohistochemistry and qPCR,” the investigators wrote.
“Gestational Δ9-THC exposure resulted in pups born with symmetrical fetal growth restriction, with catch up growth by post-natal day (PND)21. During pregnancy there were no changes to maternal food intake, maternal weight gain, litter size, or gestational length. E19.5 placentas from Δ9-THC-exposed pregnancies exhibited a phenotype characterized by increased labyrinth area, reduced Epcam expression (marker of labyrinth trophoblast progenitors), altered maternal blood space, decreased fetal capillary area and an increased recruitment of pericytes with greater collagen deposition, when compared to vehicle controls. Further, at E19.5 labyrinth trophoblast had reduced glucose transporter 1 (GLUT1) and glucocorticoid receptor (GR) expression in response to Δ9-THC exposure. In conclusion, maternal exposure to Δ9-THC effectively compromised fetal growth, which may be a result of the adversely affected labyrinth zone development. These findings implicate GLUT1 as a Δ9-THC target and provide a potential mechanism for the fetal growth restriction observed in women who use cannabis during pregnancy.”
“This data supports clinical studies that suggest cannabis use during pregnancy is associated with low birth weight babies. Clinical data is complicated because it is confounded by other factors such as socioeconomic status,” said Dan Hardy, PhD, associate professor at Western’s Schulich School of Medicine & Dentistry and co-author on the paper. “This is the first study to definitively support the fact that THC alone has a direct impact on placental and fetal growth.”
The research team was also able to characterize how THC prevents oxygen and nutrients from crossing the placenta into the developing fetus. By studying human placental cells, the researchers found that exposure to THC caused a decrease in a glucose transporter called GLUT-1. This indicates that the THC is preventing the placental transfer of glucose from the mother to the fetus. They also found a reduction in placental vasculature in the rat model suggesting reduced blood flow from the mother to the fetus. The scientists say both of those factors are likely contributing to the growth restriction that they observed in the offspring.
The team pointed out that there are currently no clear guidelines from Health Canada on the use of cannabis in pregnancy and some studies have shown that up to one in five women are using cannabis during pregnancy to prevent morning sickness, for anxiety, or for social reasons.
“Marjiuana has been legalized in Canada and in many states in the United States, however, its use during pregnancy has not been well studied up until this point. This study is important to support clinicians in communicating the very real risks associated with cannabis use during pregnancy,” said David Natale, PhD, associate professor at Queen’s and co-author on the paper.
