Whole Transcriptome Analysis of the Mouse Placenta Following Radiation-Induced Growth Restriction

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.