Placental development and function can be disrupted by maternal exposure to toxic substances which can ultimately result in poor fetal outcomes. Between June 2022 and June 2023 rural Queensland families (n=80) expecting an Australian Indigenous baby (co-designed with the Australian Indigenous Butchulla people) were enrolled in a prospective observational study to assess the impact of tobacco, nicotine and cannabis exposure on placental pathology. We surprisingly discovered placentas retrieved from pregnancies affected by exposure to cannabis smoke contained fatty deposits (steatosis). Following this unexpected observation, we conducted a scoping review (performed in accordance with PRISMA guidelines) to determine if cannabis use had previously been linked to placental steatosis.
The scoping review identified 43 relevant articles published between 1975-2022. Gestational diabetes and obesity were the most common risk factors associated with placental steatosis. No sources were found to link placental lipid accumulation to maternal cannabis use.
Candidate based gene expression analysis (real-time PCR (qRT-PCR), n = 20) was then performed on genes of interested identified through the scoping review. This analysis revealed that maternal cannabis use was associated with an increased mean expression of lipid-associated genes including PPARγ and PLIN2 compared to non-users. Other genes involved in lipogenesis and adipogenesis including LXRα, ANGPLT4, CEBPB, FASN, SCD-1 and, FABP4 also showed mean increased expression in the cannabis usage group.
Placental steatosis is not often reported, and we were unable to find any previous cases of placental steatosis associated with maternal cannabis use. It is likely that placental lipid accumulation is under-reported due to shortfalls in routine analysis of placental pathology which cannot detect lipids in paraffin-processed histology sections. The molecular characterisation undertaken here supports the conclusion that maternal cannabis use induces placental steatosis, and future work is underway to further validate these findings through ontological methods.