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bioRxiv · 10.1101/2025.09.30.678116

Effects of combined prenatal exposure to air pollution and maternal stress on immune and dopaminergic gene expression in the gut-brain axis

Martin, E. M.·Morales, M. J.·Li, N. Y.·Stoehr, M. C.·Kern, M. J.·Winters, M. F.·Smith, C. J.
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Abstract

Air pollution and maternal stress during pregnancy are both risk factors for neurodevelopmental disorders and often converge on the same communities. Epidemiological and animal studies suggest that maternal psychosocial stress may worsen the effects of air pollutants on neurodevelopmental outcomes. Previous work utilizing a mouse model of combined prenatal exposure to diesel exhaust particles (DEP) and maternal stress (MS) has found numerous sex-specific effects of DEP/MS exposure on neuroimmune outcomes, dopamine receptors, the gut-brain axis, and social behavior. However, it is unclear how broadly the immune landscape is shifted in the brain and intestinal epithelium following DEP/MS. Here, we analyzed immune gene expression in 5 brain regions important for social behavior and in 3 regions of the intestinal epithelium in both male and female offspring following either DEP/MS or control exposure. We found several interesting overall patterns. First, changes in expression of immune genes such as CD11b and Tlr4 were concentrated in the nucleus accumbens and hippocampus. Tlr4 and Il-17ra mRNA also increased in the jejunum and colon following DEP/MS, but only in females. Second, in the nucleus accumbens, catecholamine-O-methyltransferase (Comt) and dopamine transporter 1 (Slc6a3) gene expression were increased following DEP/MS indicating increased dopamine degradation at and reuptake from the synapse, respectively. Additionally, Drd2 mRNA was decreased following DEP/MS in males. Finally, we observed numerous sex differences in immune gene expression regardless of treatment in both the brain and gut. Together, these findings suggest the nucleus accumbens is a key site for neuroimmune and dopaminergic changes following DEP/MS exposure and indicate persistent female-specific changes in intestinal immunity following these prenatal exposures. HighlightsO_LICd11b and Tlr4 mRNA is altered in the NAc and Hipp following DEP/MS C_LIO_LISeveral genes indicate reduced dopamine signaling in the NAc following DEP/MS in both sexes C_LIO_LIIntestinal Tlr4 and IL-17ra mRNA is increased in females only following DEP/MS C_LI

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Martin, E. M., Morales, M. J., Li, N. Y., Stoehr, M. C., Kern, M. J., Winters, M. F., Smith, C. J.. 2025-10-01. Effects of combined prenatal exposure to air pollution and maternal stress on immune and dopaminergic gene expression in the gut-brain axis. https://doi.org/10.1101/2025.09.30.678116

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