# Impact of mild traumatic brain injury (mTBI) on sperm genome integrity: insights from a mouse model

## TL;DR

This study shows that mild traumatic brain injury in mice affects sperm genome integrity, with changes resembling aging and potential non-Mendelian effects on offspring.

## Contribution

The study reveals novel insights into how mTBI impacts sperm telomeres and gene regulation, suggesting potential heritable effects.

## Key findings

- A single mTBI event reduces sperm telomere length acutely, with increases observed in the chronic phase.
- Altered transcription of genes like Rad51, Exo1, and RNaseH1/2 correlates with TERRA levels after mTBI.
- Findings suggest mTBI may induce non-Mendelian effects with implications for offspring health.

## Abstract

Traumatic Brain Injury (TBI) poses a significant global health burden, with Mild TBI (mTBI) being the most prevalent form. TBI triggers activation of the hypothalamic–pituitary–adrenal (HPA) axis, which in turn affects the hypothalamic-pituitary–gonadal (HPG) axis regulating oogenesis and spermatogenesis. In this study, we investigated the impact of mTBI on sperm genome integrity using a repetitive mTBI (r-mTBI) mouse model.

We assessed sperm telomere length (TL), free TERRA (fTERRA), and DNA/RNA hybrid TERRA (hTERRA) levels, alongside transcriptional changes in genes involved in TERRA regulation and DNA damage response.

Our findings reveal that a single mTBI event leads to a significant reduction in sperm TL during the acute phase, followed by an increase in TL during the chronic phase of r-mTBI, reminiscent of aging-associated changes. Moreover, we observed alterations in the transcription levels of Rad51, Exo1, Rb1, RNaseH1, and RNaseH2 genes, particularly in association with fTERRA and hTERRA levels, following mTBI.

Understanding the potential non-Mendelian effects of TBI holds promise for elucidating TBI pathogenesis, mechanisms of TBI-induced diseases, and conditions of unknown etiology. Given the risks associated with repeated TBI exposure, especially in sports like football and boxing, consideration of potential paternal transmission of effects to offspring is crucial.

The online version contains supplementary material available at 10.1007/s40618-025-02549-w.