Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta’s role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta’s role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta’s crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

High doses of ionizing radiation during prenatal development can cause growth restriction, or a decrease in growth of the developing offspring. This outcome of intrauterine growth restriction (IUGR) can predispose the offspring to lifelong health outcomes, which is referred to as developmental programming. The role of the placenta in radiation-induced IUGR was investigated using a mouse model. Pregnant BALB/cAnNCrl mice were externally irradiated with 1.82 Gy x-ray irradiation on gestational day 14.5. Fetoplacental units were collected on gestational day 18.5, and growth restriction was observed in irradiated offspring. Whole placenta samples from growth restricted and sham-irradiated groups were analyzed via RNA-sequencing analysis. Differential gene expression (DEG) analysis revealed a total of 166 DEGs in the irradiated samples. Validation of these DEG findings were completed using RT-qPCR analysis. Gene ontology (GO) analysis of the DEGs supported the involvement of autoimmune response and dysregulation in retinol (vitamin A) metabolism in the placenta. Upstream prediction analysis identified a number of potential regulators responsible for the DEG profiles including Nppb, Myod1 and genes of the classic complement system (Complement C1q chains C1qa, C1qb, C1qc). Overall, these findings present an overview of the dysregulation in the mouse placenta following an acute, high-dose radiation exposure.

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.