How a father’s choices may be packaged and passed down in sperm RNA

Summary

In March 2025, in a preprint uploaded to biorxiv.org, Mansuy and colleagues reported that EVs in mice can transport certain RNAs, metabolites and lipids linked to early-life stress from circulating blood to sperm, with consequences for offspring. The offspring produced by these sperm cells had stress-related metabolic dysfunction as adults and bore the stress signatures in their own sperm RNA. “These changes imply a mechanistic link between sperm RNA modifications and phenotypic features in the offspring,” Mansuy’s team concluded in their paper, which has not yet been peer-reviewed. Phenotypic Translation Perhaps the trickiest step to understand is how sperm-borne molecules could influence an adult’s observable traits. In one form of experiment, researchers extract all the sperm RNA from mice that have been raised under stressful or health-altering conditions. Those isolated RNAs are then injected into a zygote. Pups that emerge usually “get the dad’s phenotypes,” Conine said, suggesting that the RNAs alone confer traits from dad to offspring. But how? During early development, epigenetic processes reign. As one fertilized cell divides into two, and those cells divide again, and so on, one set of DNA instructions is dynamically and repeatedly reprogrammed. The growing body specializes into different cell types and is sculpted into a sequence of increasingly complex forms. It’s possible, then, that early epigenetic alterations to the genome could have significant downstream effects on an adult. A team of researchers, including Xin Jin (top) and Xi Chen of Nanjing University, traced the epigenetic effects of paternal exercise in mice. Research out of Conine’s lab, published in 2024, showed that sperm microRNAs alter gene expression in mouse embryos. Experiments like these, he said, support the idea that offspring can inherit paternal traits via the transfer of non-DNA molecular stowaways in sperm. The recent Cell Metabolism paper took this idea a step further by traci...