Paternal immune activation-induced alteration of 28S rRNA-derived small RNAs in sperm reprograms offspring phenotypes.

ABSTRACT: Parental environmental exposures can induce transgenerational effects through epigenetic modifications in germ cells. Although paternal immune activation is implicated in transgenerational metabolic and neuropsychiatric disorders, the germline-encoded molecular vectors mediating this inheritance remain poorly understood. Here, we demonstrated that lipopolysaccharide-induced immune activation dynamically upregulated the abundance of 28S ribosomal RNA-derived small RNAs (28S-rsRNAs) in mouse sperm in a time-dependent manner. Furthermore, epididymal sperm maturation exhibited heightened susceptibility to acute immune perturbations compared with spermatogenic processes, and 28S-rsRNAs were selectively incorporated during their transit through the caput epididymis. Strikingly, zygotic microinje

SUBMITTER: Li C 

PROVIDER: S-EPMC12797211 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature