Fathers’ health influences offspring through sperm RNAs

A study in mice on small RNAs in sperm helps explain how the health of fathers can influence the health of their offspring. Bin He and colleagues explored how paternal immune activation in mice affects a specific class of small RNAs in sperm, known as 28S-rsRNAs. Mice were injected with lipopolysaccharides derived from the bacteria Escherichia coli, to prompt an immune response. A week later, the mice were found to have fewer sperm and an increased number of 28S-rsRNAs in what sperm they did have. Notably, these effects largely subsided six weeks post-injection—spanning a complete spermatogenic cycle—suggesting that the process likely occurs during sperm maturation in the caput epididymis. To explore the consequences of elevated 28S-rsRNAs, the authors microinjected synthesized 28S-rsRNAs into mouse zygotes. Male offspring developed from these zygotes displayed increased body size, a higher fat-to-muscle ratio, and impaired insulin sensitivity compared to the control group. The male offspring also exhibited heightened anxiety-like and aggressive behaviors in standard behavioral tests, accompanied by abnormal gene expression in the hippocampus. The results suggest 28S-rsRNAs act as epigenetic mediators that transmit paternal immune activation signals, causing metabolic and neurobehavioral disorders in offspring. According to the authors, the findings could aid in the development of diagnostic and therapeutic strategies to break intergenerational chains of ill health.