Placental transcriptomics reveals alterations in metabolic and transport gene programs following prenatal cannabis smoke exposure
- 1McMaster University
Abstract
Background: Prenatal cannabis use is increasing, yet the effects of inhaled cannabis smoke on placental molecular function remain poorly defined. Objective: To characterize placental transcriptomic alterations following prenatal cannabis smoke exposure using a physiologically relevant murine inhalation model. Methods: Timed-pregnant CD-1 mice were exposed to cannabis cigarette smoke or room air from embryonic day (E)6.5 to 18.5. Placentae were collected at E18.5 for microarray-based transcriptomic profiling. Differential gene expression was assessed using fetal sex adjusted linear models and false discovery rate correction. Gene set variation and ranked pathway enrichment were performed to evaluate compartment-associated and biological transcriptional programs. Selected genes were validated by quantitative PCR. Results: Large-scale transcriptomic profiles revealed no clear visual clustering by exposure; however, 23 genes were differentially expressed (FDR <0.05, |log2 fold change| > 0.5). Labyrinth-associated transcriptional signatures were reduced, whereas junctional-associated signatures were increased in exposed placentae. Pathway analyses revealed negative enrichment of fatty acid metabolism, bioenergetic, and transmembrane transport pathways, alongside positive enrichment of RNA processing and transcriptional-regulatory pathways. Quantitative PCR confirmed altered expression of multiple transport-related genes. Electron transport chain-associated gene expression was altered despite preserved placental respiratory measurements. Conclusions: Prenatal cannabis smoke exposure is associated with subtle yet coordinated placental transcriptional alterations involving metabolic, transport-associated, and gene-regulatory pathways, alongside compartment-associated transcriptional shifts. These findings provide insight into placental responses to whole cannabis smoke exposure and identify pathways that may contribute to altered placental function during pregnancy.
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BibTeX
@misc{monaco2026placental,
title = {{Placental transcriptomics reveals alterations in metabolic and transport gene programs following prenatal cannabis smoke exposure}},
author = {C. Monaco and T. Podinic and D. Xhuti and J. Feeney and D. Tan and M. Lemaire and A. MacAndrew and M. Sunil and J. P. Nederveen and S. L. Wilson and E. Ratcliffe and S. Raha},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748443},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748443v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Placental transcriptomics reveals alterations in metabolic and transport gene programs following prenatal cannabis smoke exposure
AU - C. Monaco
AU - T. Podinic
AU - D. Xhuti
AU - J. Feeney
AU - D. Tan
AU - M. Lemaire
AU - A. MacAndrew
AU - M. Sunil
AU - J. P. Nederveen
AU - S. L. Wilson
AU - E. Ratcliffe
AU - S. Raha
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748443
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748443v1
AB - Background: Prenatal cannabis use is increasing, yet the effects of inhaled cannabis smoke on placental molecular function remain poorly defined. Objective: To characterize placental transcriptomic alterations following prenatal cannabis smoke exposure using a physiologically relevant murine inhalation model. Methods: Timed-pregnant CD-1 mice were exposed to cannabis cigarette smoke or room air from embryonic day (E)6.5 to 18.5. Placentae were collected at E18.5 for microarray-based transcriptomic profiling. Differential gene expression was assessed using fetal sex adjusted linear models and false discovery rate correction. Gene set variation and ranked pathway enrichment were performed to evaluate compartment-associated and biological transcriptional programs. Selected genes were validated by quantitative PCR. Results: Large-scale transcriptomic profiles revealed no clear visual clustering by exposure; however, 23 genes were differentially expressed (FDR <0.05, |log2 fold change| > 0.5). Labyrinth-associated transcriptional signatures were reduced, whereas junctional-associated signatures were increased in exposed placentae. Pathway analyses revealed negative enrichment of fatty acid metabolism, bioenergetic, and transmembrane transport pathways, alongside positive enrichment of RNA processing and transcriptional-regulatory pathways. Quantitative PCR confirmed altered expression of multiple transport-related genes. Electron transport chain-associated gene expression was altered despite preserved placental respiratory measurements. Conclusions: Prenatal cannabis smoke exposure is associated with subtle yet coordinated placental transcriptional alterations involving metabolic, transport-associated, and gene-regulatory pathways, alongside compartment-associated transcriptional shifts. These findings provide insight into placental responses to whole cannabis smoke exposure and identify pathways that may contribute to altered placental function during pregnancy.
ER -