Identifying established human placental markers of schizophrenia in rodents after gestational ∆9-tetrahydrocannabinol exposure†.
Andrea M Kocsis, Enzo Perez-Valenzuela, Mar Rodríguez-ruiz, Mohammed H Sarikahya, Anubha Dembla, David R C Natale, Steven R Laviolette, Daniel B Hardy
Biology of reproduction January 11, 2026 DOI: 10.1093/biolre/ioaf191 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Prenatal THC-exposed rat offspring, human BeWo cells, and patient-derived cerebral organoids |
| Measures | pre-pulse inhibition of the acoustic startle response |
| Topics | Cannabis |
| Keywords | Dohad Fetal growth restriction Placenta Schizophrenia scz δ9-Tetrahydrocannabinol THC |
| Key points | Prenatal THC exposure reduced fetal weights and altered placental expression of genes previously associated with schizophrenia, with some changes being sex-specific. A subset of these genes was also altered in human BeWo cells and adult offspring brains, where increased Furin, Rps10, and Rccd1 coincided with schizophrenia-like behavior. THC also upregulated FURIN in human cerebral organoids. |
Abstract
Placental complications resulting in fetal growth restriction have been associated with dysregulated placental gene expression tied to an increased risk of schizophrenia. In rat offspring, it has been demonstrated that ∆9-tetrahydrocannabinol exposure in pregnancy results in fetal growth restriction and schizophrenia-like phenotypes (e.g., decreased pre-pulse inhibition of the acoustic startle response). However, it remains elusive if prenatal ∆9-tetrahydrocannabinol exposure induces this schizophrenia signature of placental gene expression. Therefore, our objective was to determine if these established predictive markers of schizophrenia are altered in a preclinical model of gestational oral ∆9-tetrahydrocannabinol exposure in rodents. We observed significantly reduced fetal weights in male and female prenatal ∆9-tetrahydrocannabinol-exposed offspring in the absence of maternal pregnancy outcomes. Placentae from ∆9-tetrahydrocannabinol-exposed males and females revealed altered expression of genes previously identified in human transcriptomic datasets of schizophrenia (i.e., Furin, Rccd1, and Atp5mk), with some expression changes being sex-specific (i.e., Eif5, Rps10, Vps33b, and Iqgap1). A subset of these genes were found differentially expressed in human BeWo cells exposed to ∆9-tetrahydrocannabinol. Targets were next examined in the adult rodent (postnatal day70) brain, and a subgroup of these genes (i.e., Furin, Rps10, and Rccd1) were increased concomitant with schizophrenia-like behavior (e.g., decreased pre-pulse inhibition). We further detected ∆9-tetrahydrocannabinol-induced upregulation of FURIN in patient-derived cerebral organoids, an effect observed in both control and schizophrenia cell lines. Collectively, these findings demonstrate prenatal ∆9-tetrahydrocannabinol exposure can lead to altered gene expression in established prioritized markers of schizophrenia in the placenta in both animal and human models.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 3
- Cannabis and Psychosis Through the Lens of DSM-5 International Journal of Environmental Research and Public Health October 28, 2019
- Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus. Neurobiology of Disease July 1, 2024
- Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry. eNeuro 2022