In utero optical coherence tomography reveals changes in murine embryonic brain vasculature after prenatal cannabinoid exposure

Abstract

Prenatal substance abuse is a major public health concern. Much research has been focused on alcohol and other drug use, but there is a lack of information about prenatal cannabinoid use. Nevertheless, marijuana use during pregnancy increases the risk of a stillbirth by approximately 2.3X. Synthetic cannabinoids (SCB) are a group of heterogeneous compounds which were developed to understand the endogenous cannabinoid system and as potential therapeutics. SCBs are legally available for purchase in several places, and the use of natural and synthetic cannabinoids is high among women of reproductive age. Combined with the prevalence of unplanned pregnancies, the high use of cannabinoids may lead to an increase in prenatal exposure to cannabinoids. Early studies have shown morphological and behavioral anomalies similar to fetal alcohol syndrome. Even though the mechanisms of Δ9 -tetrahydrocannabinol (Δ9 -THC), the major psychoactive component of marijuana, and SCB are similar, there are several important differences. Subsequently, some SCBs have a 40 to 600 fold higher potency than Δ9 -THC. However, there is paucity of research focused on the prenatal effects of SCBs. This study uses correlation mapping optical coherence tomography (cm-OCT) to evaluate acute changes in the murine fetal brain vasculature in utero after exposure to CP-55,940, a well-characterized and commonly used reference compound in cannabinoid research. Our results showed a rapid decrease in parameters quantifying vasculature, i.e., vessel area density, and vessel length fraction, as compared to the sham group, demonstrating a dramatic and rapid effect of cannabinoids on fetal brain vasculature. Our work shows the need for further research on the effects of cannabinoids on fetal development.