Transcriptomic Analysis of CBD-Exposed Rat Placentae Reveals Down-Regulated Angiogenic Pathways and Up-Regulated Metabolic Processes
Bibliographic record
Abstract
Following nicotine, cannabis is the most used drug during pregnancy. In utero cannabis exposure is linked to adverse outcomes, including fetal growth restriction. Cannabidiol (CBD), the non-hallucinogenic constituent of cannabis, is perceived as safe for use during pregnancy by ~25% of women. While studies assessing the effects of Δ-9-THC, the other principal cannabinoid in cannabis, have been initiated, research examining the impact of CBD on pregnancy is scarce. The placenta facilitates the exchange of gas, nutrients and waste between the fetus and mother. Our group has recently identified altered placental morphology and reduced fetal growth after in utero CBD exposure in rats. However, the influence of CBD on genes, transcription factors and biological processes in the placenta has not been assessed. This study aimed to identify biological pathways in the placenta that were significantly altered by CBD-exposure and correlate the findings with previously performed histological analysis. Pregnant rats were administered a daily dose of 3 mg/kg CBD or a vehicle control from embryonic day (E) 6.5-18.5. On E19.5, placentae were harvested for transcriptomic analysis. RNA extraction, library construction and bulk RNA sequencing was performed by Genome Quebec. The top differentially expressed genes were analysed using Metascape software, revealing the most up- and down-regulated Gene Ontology (GO) biological process pathways. Down-regulated GO biological processes included tube morphogenesis, angiogenesis, and blood vessel morphogenesis, which supported the angiogenic complications identified by histology. Further, the most significantly up-regulated GO biological processes were metabolic, including peptide, glycoprotein, glycosaminoglycan, and tetrahydrofolate. This is significant, as the histological analysis identified elevated Glut3 expression in the placentae from CBD-exposed pregnancies. Elevated Glut3 in fetal growth restriction is associated with changes to metabolic pathways. Consequently, additional studies will include analysis of CBD-exposed rat trophoblast cells to establish whether metabolic changes may underlie the altered morphology identified in CBD-exposed placentae.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".