Stability of germline structural variation under dietary and ethanol challenges

Abstract Environmental and lifestyle factors can modify the sperm epigenome and influence offspring phenotype, yet whether such exposures directly affect structural variation in the male germline remains unclear. Structural variants (SVs) arise primarily through replication-associated mechanisms and represent a major source of genomic diversity and disease risk. Here, we tested whether three physiologically relevant exposures - a Western diet, a low-protein diet, and chronic ethanol consumption - alter germline SV profiles in mice. Using optical genome mapping, we analyzed paired sperm and kidney samples from individual animals, enabling within-mouse comparisons between germline and somatic tissues. Across all conditions, putative de novo SVs constituted ∼7% of detected variants, with comparable proportions in sperm and kidney. No significant differences were detected between experimental and control groups in SV count, size distribution, variant allele fraction, or zygosity in either tissue. A genome-wide scan identified a small number of candidate loci with nominal SV frequency differences in Western diet-exposed sperm, none of which remained significant after multiple-testing correction. Together, these results indicate that common dietary and alcohol-related exposures do not induce detectable global changes in germline structural variation, suggesting that any environmental effects on SV formation are at most subtle or highly localized.