Sperm as a multilayered epigenetic information system: encoding and transmission of paternal environmental signals

Spermatozoa are increasingly recognized as carriers of non-genetic paternal information, rather than passive vehicles for the haploid genome. During spermatogenesis and post-testicular epididymal maturation, the paternal germline establishes a compact but functionally organized epigenome composed of DNA methylation, retained histones and histone modifications, chromatin-associated factors, and diverse small RNAs. These layers are environmentally responsive. In animal models, paternal diet, stress, toxicant exposure, and inflammatory or microbiome-related challenges can alter sperm DNA methylation, chromatin states, and small RNA cargo, with many changes mapping to loci involved in development, metabolism, and stress-response pathways. After fertilization, the paternal genome undergoes extensive epigenetic reprogramming; nevertheless, a subset of DNA methylation and chromatin features can resist erasure or be functionally relayed, while sperm-derived RNAs can influence early embryonic gene expression. Recent work, including studies of diet-induced sperm mitochondrial tRNAs, further supports the concept that defined paternal exposures may be transmitted to the embryo through discrete RNA-mediated mechanisms. In humans, lifestyle and environmental exposures are associated with measurable sperm epigenomic variation and with offspring health outcomes, but most evidence remains observational and is vulnerable to confounding by genetics, maternal factors, and shared environments. A central challenge is therefore to connect specific sperm epigenetic alterations to molecular effects in the early embryo and to subsequent offspring phenotypes. Here, we review how paternal environmental information is encoded during spermatogenesis and epididymal maturation, reshaped by environmental exposures, and interpreted by the early embryo, emphasizing multilayer integration and the evidence required to move from association to mechanism.