Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse
Open accessAbstract
Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations.
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In utero exposure to concentrated ambient ultrafine particles from gestation days 0.5-16.5 resulted in ventriculomegaly, increased corpus callosum area, and reduced hippocampal area in male and female offspring.
“Exposure to concentrated ambient ultrafine particles from gestation days 0.5-16.5 also resulted in ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in male and female offspring.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [61]
The Abstract reports exposure on gestation days 0.5–16.5 and the three stated brain changes in both sexes. However, it describes the exposure as concentrated ambient fine and ultrafine particles, not ultrafine particles alone; the Animals and Air Pollution Exposures section likewise places the particle sizes in the fine/ultrafine range. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBoth sexes demonstrated increased microglial activation, reduced total corpus callosum microglia number, and corpus callosum hypermyelination after in utero ultrafine PM exposure.
“Both sexes demonstrated increased microglial activation and reduced total CC microglia number and CC hypermyelination.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [61]
The Microglial Activation results report increased corpus callosum (CC) microglial activation in both sexes, but a statistically significant reduction in total CC microglia only in males; the reduction in females was a trend (P = .09). The Myelination results support increased CC myelin staining in both sexes. The exposure was to concentrated ambient fine and ultrafine particles, not ultrafine particles alone. (LLM, conf=0.88)
Experimental — accuracy not yet measuredUsing the VACES system, Klocke et al. generated an average concentration of 92.69 ± 19.16 (SD) μg/m3, and Church et al. produced average levels of 135.8 ± 13.17 μg/m3, representing 11 times ambient air concentrations.
“Using the VACES system, Klocke et al. [61] generated an average concentration of 92.69 ± 19.16 (SD) μg/m3, and Church et al. [63] produced average levels of 135.8 ± 13.17 μg/m3, representing 11 times ambient air concentrations.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [61]
Corpus callosum iron deposition was increased in female offspring after in utero ultrafine PM exposure.
“CC iron (Fe) deposition was increased in female offspring.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [61]
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Research Progress on the Correlation Between Atmospheric Particulate Matter and Autism
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Sobolewski, M., Conrad, K., Marvin, E., Eckard, M. L., Goeke, C. M., Merrill, A. K., Welle, K. A., Jackson, B. P., Gelein, R. M., Chalupa, D., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20461899
Self-citationDeSerisy, M. L., Wong, D., Yang, H., Cohen, J. W., Pagliaccio, D., Herbstman, J. B., Rauh, V., Perera, F. P., & Margolis, A. E. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1737011
- Authors
- Klocke, C., Allen, J. L., Sobolewski, M., Mayer-Pröschel, M., Blum, J. L., Lauterstein, D., Zelikoff, J. T., & Cory-Slechta, D. A.
- Affiliations
- New York University (US)
- Corresponding author
- Klocke, Carolyn
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01-13
- Volume
- 156
- Issue
- 2
- Pages
- kfx010
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- PMC
- PMC6074840
- OpenAlex
- W2573443486
- Cited by
- 87
- References
- 97
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 14 · 2023: 7 · 2022: 15 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 7 · 2017: 3
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Toxicological Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- March of Dimes Foundation (ES07026, 21-F12-13)
- National Institute of Environmental Health Sciences (R01ES025541, P30ES000260, P30ES001247, T32ES007026)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- ultrafine particles, fine particles, particulate matter, brain development, ventriculomegaly, microglial activation, iron accumulation, sex differences, neurodevelopmental disorders, autism spectrum disorder, mouse embryo
- MeSH terms
- Air Pollutants, Animals, Brain, Female, Gestational Age, Male, Organ Size, Pregnancy, Prenatal Exposure Delayed Effects, Mice, Particulate Matter, Neurodevelopmental Disorders
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