Adverse effects of gestational ?9-tetrahydrocannabinol exposure on the embryonic germline transcriptome and metabolome

An increasing number of women report cannabis use during their pregnancy, with little knowledge on the repercussions of such an exposure onto early embryonic processes. In particular, exposure to the most abundant phytocannabinoid, ?9-tetrahydrocannabinol (?9-THC), could alter the development of embryonic germ cells, with potential consequences across generations. Here, we extensively characterized the impact of gestational exposure to ?9-THC onto the developmental trajectory of an in vitro model for primordial germ cells. Our data reveals that ?9-THC exposure increases glycolytic rates in embryonic stem cells, with consequences on their proliferation. We further show that, in the absence of continuous exposure, ?9-THC has long-lasting adverse consequences on the metabolome and transcriptome of embryonic germ cells. These results constitute the first characterization of the impact of gestational ?9-THC exposure onto the embryonic germline. Overall design: Comparative gene expression profiling analysis of RNA-seq data for ESCs, EpiLCs, PGCLCs treated with 100nM of ?9-THC or with the vehicle as a control