Courville, A. | Search bioRxiv

bioRxiv2026

Prenatal cannabinoid exposure induces sex-specific alterations in placental growth and lipid metabolism gene expression

BackgroundPrenatal cannabis use is becoming increasingly more commonplace. However, cannabis exposure is linked to adverse pregnancy outcomes, including gestational hypertension, preeclampsia, and preterm birth. The aim of this study was to determine the morphological and molecular effects of prenatal cannabinoid exposure on the placenta. MethodsPregnant Sprague-Dawley rats were exposed daily to vaporized THC (100 mg/mL) starting at gestational day (GD)5 until GD19 when dams were sacrificed and fetuses and placentas collected. Fetuses were genotyped for genetic sex and transcriptomic analysis was performed on male and female THC-exposed and control placentas. ResultsOn GD19, both the fetuses and placentas from the THC group were significantly larger than the control. When separated by sex, both male and female THC fetuses were significantly larger; however, only male THC placentas were significantly larger than male control placentas with no significant difference in placental weight between female control and THC placentas. RNA-sequencing revealed enriched biological processes related to nutrient transport and lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling and organization. Further transcriptomic analysis determined that the differentially expressed genes and enriched biological processes related to lipid metabolism were preferentially enriched in the female THC placentas compared to the male, suggesting a sex-specific effect. DiscussionCollectively, these data present sex-specific effects of prenatal cannabinoid exposure on placental growth and global gene expression. These data also suggest that sex influences gene expression of genes related to lipid metabolism in the THC-exposed placentas.

Developmental Biology↗

bioRxiv2022

Restriction of dietary fat, but not carbohydrate, alters brain reward circuitry in adults with obesity

Weight loss diets often target restriction of dietary fat or carbohydrate, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on human brain are unclear. We investigated whether selective isocaloric reductions in dietary fat or carbohydrate altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain reward regions in response to visual food cues in 17 inpatient adults with obesity as compared to a eucaloric baseline diet. On the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain reward regions. After the reduced fat diet, ad libitum intake shifted towards foods high in both fat and carbohydrates. These results suggest that dietary fat restriction increases tonic dopamine in brain reward regions and affects food choice in ways that may hamper diet adherence.

neuroscience↗