Impact of mid-gestational Δ9-tetrahydrocannabinol exposure on hepatic development in Wistar rat offspring

Cannabis use during pregnancy is increasing globally, raising concerns about fetal exposure to Δ9- tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis. THC readily crosses the placental barrier and may disrupt the endocannabinoid system, which regulates fetal organogenesis, including hepatic development. This study investigated the effects of oral THC exposure during mid-gestation on liver morphology, growth indices, and selected biochemical markers in Wistar rat offspring. Twelve adult female Wistar rats were mated with proven fertile males, and pregnancy was confirmed by the presence of a vaginal plug and spermpositive vaginal smear, designated as gestational day (GD) 0. Pregnant rats were randomly assigned to a control group (vehicle only) or a THC-treated group (150 mg/kg, oral gavage) from GD12 to GD21. Offspring were evaluated for body weight, liver weight, histomorphological changes using haematoxylin and eosin and periodic acid–Schiff staining, and serum biochemical parameters. Prenatal THC exposure significantly increased liver weight compared with controls (p < 0.0001) and was associated with increased body weight (p = 0.0004). Histological examination revealed hepatocellular hypertrophy, cytoplasmic vacuolization, architectural disorganization, and reduced glycogen deposition in THC-exposed offspring. Biochemical analysis showed significant reductions in alkaline phosphatase (p = 0.012) and conjugated bilirubin (p < 0.0001), with significant increases in total protein (p = 0.015) and total bilirubin (p = 0.014). Oral THC exposure during mid-gestation disrupts hepatic development in Wistar rat fetuses, primarily affecting liver growth, cellular architecture, and synthetic capacity rather than inducing overt hepatocellular necrosis.

Key Words: Δ9-tetrahydrocannabinol; prenatal exposure; liver development; developmental toxicology