319 - Sex-Specific Alterations in Endocannabinoid-Lipid Gene expression in Neonates with Prenatal Cannabis Exposure

Publication Number: 3308.319

Parvathy Krishnan, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Tomoko Kaneko-Tarui, Tufts University School of Medicine, Boston, MA, United States; Kiran Singh, Tufts Medical Center, Boston, MA, United States; Marissa Chow, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Francesca Carasi-Schwartz, Floating Hospital for Children at Tufts Medical Center, Boston, MA, United States; Elizabeth Yen, Tufts Medicine Pediatrics-Boston Children's, Boston, MA, United States

Background: Cannabis has differential cardiometabolic effects in females and males. With the increasing cannabis use during pregnancy, there is a need to understand the effects of cannabis on neonatal growth and metabolic programming. The endocannabinoid system interacts with lipid-sensing transcriptional networks (PPARα, LXRα), intracellular lipid chaperones (FABP5), and cholesterol transporters (ABCA1) via cannabinoid receptors (CN1R, CN2R). Disruption of these pathways during in-utero development may alter lipid utilization, adipogenesis, and energy homeostasis, predisposing to sex-specific susceptibility to metabolic syndrome.

Objective: To examine the sex-specific effects of prenatal cannabis exposure on anthropometrics and metabolic/lipid gene expression in neonates.

Design/Methods: Saliva was collected within 24 hours of birth from 18 neonates (9 cannabis-exposed, 9 non-exposed matched by gestational age/GA and sex) to undergo transcriptomic analysis of CNR1, ABCA1, FABP5, LXRα, and PPARα. Gene expression was normalized against GAPDH and YWAHZ, with threshold cycle (Ct) values inversely proportional to gene expression levels. Maternal and demographic data included race/ethnicity, delivery method, Apgar scores, GA, sex, anthropometric measurements (birth weight/BW, head circumference/HC, length/L, and percentiles). Gene expression was correlated with anthropometric measurements using Pearson's analysis. Continuous data were analyzed using a student's t-test, categorical data using a Chi-square test. Significance was set at p< 0.05.

Results: Cannabis-exposed neonates were born smaller and with a greater proportion of small for gestational age (SGA) and low birth weight (LBW) than non-exposed neonates (p < 0.05, Table 1). Gene expression did not differ significantly by exposure, however, when stratified by sex, the expression of CNR1 and FABP5 were significantly lower in the cannabis-exposed females than males (Table 2). Correlation between BW percentiles and the expression of CNR1 and FABP5 showed opposing directions in cannabis-exposed females and males (Figure), suggesting sex-specific effects of prenatal cannabis exposure on endocannabinoid-lipid gene regulation and growth.

Conclusion(s): Our pilot data support previous studies showing the adverse effects of maternal cannabis use on neonatal growth. Sex-specific modulation of lipid metabolism affecting birth weight may be mediated by cannabis action. Larger cohorts integrating feeding behavior and longitudinal growth outcomes will clarify whether these transcriptional changes predict postnatal metabolic risk.

Table 1. Demographic and Clinical Data
NH: non-Hispanic, GBS: group B streptococcus, BMI: body mass index, SGA: small for gestational age, DOL: day of life. Data presented as mean ± standard deviation or median (interquartile ranges) for continuous measures, and n (%) for categorical measures. Bolded p values indicate significance.

Table 2. Differences in gene expression in females and males with prenatal cannabis exposure.
ΔCt (delta threshold cycle) values are in mean ± standard deviation, with values inversely proportional to gene expression levels. CNR1: cannabinoid receptor 1, ABCA1: ATP binding cassette subfamily A member 1, FABP5: fatty acid binding protein 5, LXRα: liver X receptor alpha, PPARα: peroxisome proliferator-activated receptor alpha. Bolded p values indicate significance.

Figure. CNR1 and FABP expression related to birth weight percentile in cannabis-exposed females and males.
Gene expression in ΔCt (delta threshold cycle), with values inversely proportional to gene expression levels. CNR1:
cannabinoid receptor 1, FABP5: fatty acid binding protein 5. Birth weight percentile values calculated using Fenton 2025
growth standards.