A causal atlas for sperm DNA fragmentation: separating "programmed" breaks from "acquired" injury across the male tract.

Sperm DNA fragmentation (SDF) is still treated as a single metric despite converging evidence that it is a composite of mechanistically distinct break classes. We argue for a 'causal atlas' that maps when and where damage is introduced, from spermiogenesis to epididymal transit to ejaculation, and partitions SDF into programmed vulnerability created by faulty chromatin remodeling/topoisomerase-associated events and abortive apoptosis, versus acquired injury from oxidative/enzymatic attack during transit. Although current assays cannot definitively assign SDF to a particular mechanism or anatomical stage, integrating complementary measures may support mechanistically informed patient stratification and guide the development of more targeted interventions.