Paternal Microplastic Exposure Alters Sperm Small Noncoding RNAs and Affects Offspring Metabolic Health in Mice

Microplastics (MPs) are small plastic particles emerging as significant environmental pollutants. Humans are ubiquitously exposed to MPs, and recent studies have associated MP exposure with an increased risk of chronic diseases. MPs can also be detected in both male and female reproductive tissues in humans. Parental exposure to various environmental contaminants can increase the risk of cardiometabolic disease in offspring. However, the impact of parental MP exposure on offspring health has not been studied. In the current study, we investigated the effects of paternal exposure to MPs on the metabolic health of F1 offspring in mice. Intriguingly, we found that paternal MP exposure had sex-specific effects on diet-induced obesity, including altered body compositions in high-fat-diet-fed F1 offspring. Further, female F1 descendants from MP-exposed sires had exacerbated insulin resistance. Sperm small noncoding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), may contribute to the intergenerational transmission of paternally acquired cardiometabolic disorders. We recently developed an innovative panoramic RNA display by overcoming RNA modification aborted sequencing (PANDORA-seq) method to reveal comprehensive sncRNA landscapes in sperm and other tissues. Using PANDORA-seq, we discovered that MP exposure altered sperm tsRNA and rsRNA profiles. Interestingly, several MP-stimulated tsRNAs/rsRNAs influenced the gene expression in murine embryonic stem cells in vitro, indicating a potential role of those sncRNA in contributing to paternal MP exposure-elicited offspring phenotypes. Our results suggest that parental MP exposure may have intergenerational adverse impacts on offspring's metabolic health. These findings also underscore the urgency of better understanding the health consequences of plastic exposure in humans.