High-Dose Gestational Irradiation Disrupts Fetal Mouse Brain Structure and Region-Specific Transcriptomic Profiles.
8 affiliations
- 1Medical Sciences Division, NOSM University, Sudbury, ON P3E 2C6, Canada.
- 2School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada.
- 3Medical Sciences Division, NOSM University, Thunder Bay, ON P7B 5E1, Canada.
- 4Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada.
- 5Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada.
- 6Health Sciences North Research Institute, Sudbury, ON P3E 2H3, Canada.
- 7Department of Psychology, Nipissing University, North Bay, ON P1B 8L7, Canada.
- 8Department of Child and Family Studies, Nipissing University, North Bay, ON P1B 8L7, Canada.
Abstract
Background/Objectives: Prenatal exposure to ionizing radiation can disrupt neurodevelopment, yet the region-specific structural and molecular responses of the developing brain remain incompletely understood. In particular, how gestational irradiation alters transcriptional programs across distinct fetal brain regions and whether these responses differ by sex has not been fully characterized. This study examined the structural and transcriptomic responses in the fetal mouse brain following high-dose gestational irradiation. Methods: Pregnant BALB/c mice were exposed to 1.8 Gy of X-ray irradiation on gestational day (GD) 14.5, and fetal brains were collected on GD 18.5. Results: Using a previously characterized model of radiation-induced fetal growth restriction, H&E-stained sagittal fetal brain sections revealed reduced hippocampal volume and enlargement of the lateral ventricle, while cerebellar volume and optical density were not significantly altered. RNA-seq analysis of the telencephalon, diencephalon, midbrain, and hindbrain revealed region-specific transcriptional dysregulation enriched for genes associated with immune and inflammatory signalling, neurogenesis, gliogenesis, cell migration, and neurotransmitter signalling, with the strongest response observed in the telencephalon and differing DEG profiles between males and females in sex-stratified analyses. Conclusions: These findings indicate that high-dose gestational irradiation is associated with region-specific structural alterations and transcriptional changes in the fetal brain, generating hypotheses regarding the mechanisms of radiation-induced neurodevelopmental disruption.
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BibTeX
@article{hourtovenko2026highdose,
title = {{High-Dose Gestational Irradiation Disrupts Fetal Mouse Brain Structure and Region-Specific Transcriptomic Profiles.}},
author = {Cameron Hourtovenko and Shayenthiran Sreetharan and Neelam Khaper and Simon J Lees and Christopher Thome and Douglas Boreham and Christine Lalonde and Sujeenthar Tharmalingam and T C Tai},
journal = {Genes},
year = {2026},
month = oct,
doi = {10.3390/genes17101267},
url = {https://europepmc.org/article/MED/42938383},
note = {CC BY},
}
RIS
TY - JOUR
TI - High-Dose Gestational Irradiation Disrupts Fetal Mouse Brain Structure and Region-Specific Transcriptomic Profiles.
AU - Cameron Hourtovenko
AU - Shayenthiran Sreetharan
AU - Neelam Khaper
AU - Simon J Lees
AU - Christopher Thome
AU - Douglas Boreham
AU - Christine Lalonde
AU - Sujeenthar Tharmalingam
AU - T C Tai
PY - 2026
DA - 2026/10/12
JO - Genes
DO - 10.3390/genes17101267
UR - https://europepmc.org/article/MED/42938383
AB - Background/Objectives: Prenatal exposure to ionizing radiation can disrupt neurodevelopment, yet the region-specific structural and molecular responses of the developing brain remain incompletely understood. In particular, how gestational irradiation alters transcriptional programs across distinct fetal brain regions and whether these responses differ by sex has not been fully characterized. This study examined the structural and transcriptomic responses in the fetal mouse brain following high-dose gestational irradiation. Methods: Pregnant BALB/c mice were exposed to 1.8 Gy of X-ray irradiation on gestational day (GD) 14.5, and fetal brains were collected on GD 18.5. Results: Using a previously characterized model of radiation-induced fetal growth restriction, H&E-stained sagittal fetal brain sections revealed reduced hippocampal volume and enlargement of the lateral ventricle, while cerebellar volume and optical density were not significantly altered. RNA-seq analysis of the telencephalon, diencephalon, midbrain, and hindbrain revealed region-specific transcriptional dysregulation enriched for genes associated with immune and inflammatory signalling, neurogenesis, gliogenesis, cell migration, and neurotransmitter signalling, with the strongest response observed in the telencephalon and differing DEG profiles between males and females in sex-stratified analyses. Conclusions: These findings indicate that high-dose gestational irradiation is associated with region-specific structural alterations and transcriptional changes in the fetal brain, generating hypotheses regarding the mechanisms of radiation-induced neurodevelopmental disruption.
SN - 2073-4425
ER -