Prenatal Cannabinoid Exposure Induces Sex-Specific Alterations in Fetal Growth and Placental Lipid Metabolism Gene Expression.

West R.; Courville A.; Camp C.; Drotos P.; Parker C.; Reed M. · Cannabis and cannabinoid research · 2026

**Background & Methods** This animal study examined the effects of prenatal cannabinoid exposure on placental development and gene expression in pregnant Sprague-Dawley rats. Dams received daily vaporized THC from gestational day 5 through day 19, with fetuses and placentas collected at sacrifice for morphological analysis and transcriptomic profiling stratified by fetal sex. **Key Findings** - Female fetuses exposed to prenatal THC were significantly larger than controls at gestational day 19, while male fetuses showed no significant growth differences; placental weights and fetal-to-placental weight ratios were similar between groups regardless of sex. - RNA sequencing identified enriched biological pathways in THC-exposed placentas related to nutrient transport, lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling. - Sex-specific gene expression patterns emerged, with differentially expressed genes and lipid metabolism-related pathways preferentially enriched in female THC-exposed placentas compared to male placentas, indicating sexually dimorphic placental responses to cannabinoid exposure. **Dosage & Administration** Vaporized THC at 100 mg/mL administered daily from gestational day 5 to gestational day 19 of pregnancy. **Safety & Adverse Effects** Not reported. The study focused on molecular and morphological endpoints rather than clinical adverse effects or maternal toxicity outcomes. **Evidence Quality** This preclinical animal study provides mechanistic insights into cannabinoid effects on placental development but has significant limitations for human applicability. The use of a rodent model with high-dose vaporized THC may not accurately reflect human prenatal cannabis use patterns, routes of administration, or dosing. The study is limited to endpoint evaluation at a single gestational timepoint (GD19), restricting assessment of long-term fetal development or postnatal outcomes. While transcriptomic analysis provides valuable molecular data, functional validation of identified pathways is lacking. The study does not address potential confounding factors relevant to human pregnancy or investigate mechanisms underlying the observed sex-specific effects. As a basic science investigation in animals, this research represents lower-level evidence (preclinical) requiring human clinical studies to establish clinical relevance and inform pregnancy safety guidelines.

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