# Alterations in Blood and Hippocampal mRNA and miRNA Expression, Along with Fat Deposition in Female B6C3F1 Mice Continuously Exposed to Prenatal Low-Dose-Rate Radiation and Their Comparison with Male Mice

## TL;DR

This study found that prenatal low-dose gamma radiation affected fat deposition and gene expression in female mice, with sex-specific differences in mRNA and miRNA levels.

## Contribution

The study reveals sex-specific molecular and physiological effects of prenatal low-dose-rate gamma irradiation in mice.

## Key findings

- Prenatal irradiation in female mice caused reduced organ weights and increased fat deposits in specific body areas.
- Hippocampal mRNA levels of H2bc24, Fos, Cd74, and Tent5a were upregulated in irradiated females.
- Sex-specific differences in mRNA and miRNA expression were observed in both blood and hippocampus.

## Abstract

Our recent study revealed that continuous prenatal low-dose-rate irradiation did not induce cellular changes in the dentate gyrus of the hippocampus in male B6C3F1 mice exposed to gamma rays during prenatal development. However, changes in body weight, body mass index (BMI), locomotor ability, and mRNA and miRNA expressions in the hippocampus and blood were observed. To investigate potential sex differences in the effects of prenatal gamma irradiation, we conducted a parallel study on female B6C3F1 mice. The results showed significant reductions in the weight of the lungs and left kidney in prenatally irradiated female offspring, accompanied by significantly increased fat deposits in the mesentery, retroperitoneal, and left perigonadal areas. Despite these systemic changes, no cellular alterations were observed in the subgranular zone (immature neurons) or the hilus of the dentate gyrus (mature neurons and glial cells, including astrocytes, microglia, and oligodendrocyte progenitor cells). However, significant increases in hippocampal mRNA expression were detected for genes such as H2bc24, Fos, Cd74, Tent5a, Traip, and Sap25. Conversely, downregulation of mRNAs Inpp5j and Gdf3 was observed in whole blood. A Venn diagram highlighted the differential expression of two mRNAs, Ttn and Slc43a3, between the hippocampus and whole blood. Comparisons between prenatally irradiated male and female B6C3F1 mice revealed sex-specific differences. In whole blood, 4 mRNAs (Scd1, Cd59b, Vmn1r58, and Gm42427) and 1 miRNA (mmu-miR-8112) exhibited differential expression. In the hippocampus, 12 mRNAs and 2 novel miRNAs were differentially expressed between the sexes. qRT-PCR analysis validated the upregulation of H2bc24, Fos, Cd74, and Tent5a in the female hippocampus. These gene expression changes may be associated with the increased fat deposition observed following chronic low-dose-rate gamma irradiation exposure. This study underscores the importance of investigating sex-specific biological responses to prenatal gamma irradiation and highlights potential molecular pathways linked to observed physiological changes.