Michelle T. Nguyen

Background: For Autism spectrum disorders (ASD), genetics and environmental toxins, like pollutants, can increase risk for these altered neurodevelopmental conditions.^2,3 There is emerging evidence is that particulate matter (PM), part of air pollutants, induces expression changes of miRNA that, in turn, are associated with ASD. There is an urgent need to understand the association with PM-associated miRNA changes and neurodevelopment as there is increased pollution exposure due to urbanization.⁴ miRNAs are passed down in breast milk and in the placenta and are known to be associated with normal developmental programming, growth, and immune system responses for the infant; therefore, altered miRNA composition may be a target to decrease risk of neurodevelopmental delay following in utero pollutant exposure

Objective/hypothesis: In utero (PM) exposure-associated expression changes in miRNA contribute to increased risk for neurodevelopmental delay for the fetus⁴.

Methods: PubMed was searched for articles using the keywords “miRNA”, “autism”, and “particulate matter” to identify pertinent literature. Only articles from 2017-2025 were included for review.

Results: Prenatal PM exposure is associated with miRNA expression dysregulation.^5,6 In a study examining postpartum milk miRNA expression in Latina women in California, increased cumulative pregnancy exposure to air pollutants and PM as linked to increased expression of  miR-200c-3p and miR-200b-3p.⁵ Arsenic exposure through unregulated drinking water was significantly associated with lower miRNA levels in breast milk, specifically miR-182-5p and miR-152-3p.⁶  PM exposure is linked to childhood neurodevelopment delays.⁷ Children with lower scores on the Mullen Scales of Early Learning visual reception domain, a testing paradigm for ASD and other neurodevelopmental delays, displayed higher levels of prenatal PM exposure.⁷ Childhood neurodevelopmental delays may be associated with PM-induced miRNA expression changes.  miR-3168, the most upregulated in miRNA in preterm breast milk exosomes compared to that of term and was associated with decreased neuronal growth in vitro.⁸ Prenatal PM_2.5 exposure to metals such as lead, aluminum, vanadium, and tin was inversely correlated to Ages and Stages Questionnaire test scores for communication, problem solving, and personal-social social domains.⁴  Overall, these data suggest relationships between in utero pollutant exposure and neurodevelopmental delay through miRNA expression; however, critical exposure periods not agreed upon.^5,7 While the first trimester may be a sensitive window for PM exposure-induced miRNA expression changes,⁵ individuals with altered neurodevelopment may also have a critical exposure window in the third trimester and first year of life. PM exposures during these later stages were was associated with lower scores for the Vineland Adaptive Behavior Scale daily living skills and socialization domains in children with ASD.⁷ This may be because of a reserve ability to adapt/recover from PM damage late in pregnancy does not occur for children with ASD.

Conclusion: Research shows that miRNAs are affected by PM and that PM exposure is associated with neurodevelopmental delay.⁵/30/25 9:29:00 PM The first trimester may be a sensitive window for overall PM-induced miRNA changes in neurodevelopment, while in later trimesters, PM-induced miRNA changes can impact individuals with ASD. More research is needed to confirm susceptible windows of PM induced miRNA changes and their specific effects.^5,7

Works Cited:

1. Yi DY, Kim SY. Human Breast Milk Composition and Function in Human Health: From Nutritional Components to Microbiome and MicroRNAs. Nutrients. 2021;13(9):3094. doi:10.3390/nu13093094
2. Wang L, Wang B, Wu C, Wang J, Sun M. Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy. Int J Mol Sci. 2023;24(3):1819. doi:10.3390/ijms24031819
3. Genovese A, Butler MG. The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations. Genes. 2023;14(3):677. doi:10.3390/genes14030677
4. Wang P, Zhou Y, Zhao Y, et al. Prenatal fine particulate matter exposure associated with placental small extracellular vesicle derived microRNA and child neurodevelopmental delays. Sci Total Environ. 2022;841:156747. doi:10.1016/j.scitotenv.2022.156747
5. Holzhausen EA, Kupsco A, Chalifour BN, et al. Human milk EV-miRNAs: a novel biomarker for air pollution exposure during pregnancy. Environ Res Health. 2023;1(3):035002. doi:10.1088/2752-5309/ace075
6. Howe CG, Armstrong DA, Muse ME, et al. Periconceptional and Prenatal Exposure to Metals and Extracellular Vesicle and Particle miRNAs in Human Milk: A Pilot Study. Expo Health. 2023;15(4):731-743. doi:10.1007/s12403-022-00520-1
7. McGuinn LA, Wiggins LD, Volk HE, et al. Pre- and Postnatal Fine Particulate Matter Exposure and Childhood Cognitive and Adaptive Function. Int J Environ Res Public Health. 2022;19(7):3748. doi:10.3390/ijerph19073748
8. Ma L, Huo Y, Tang Q, et al. Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment. Mol Nutr Food Res. 2024;68(9):e2300113. doi:10.1002/mnfr.202300113