Figure 1

Schematic representation of the testicular and epididymal events leading to the drastic change in sperm chromatin organization. During spermatogenesis which takes place within the epithelium of the seminiferous tubule (boxed area in the schematized testis) sequential post-translational modifications of histones occur as well as insertion of testicular-specific histone variants. These events precede the replacement of most histones by transition proteins (TNPs) which in turn at the end of the spermatogenetic program (ie. spermiogenesis) will be replaced by protamines (PRMs). These modifications allow for the compaction of the majority of the sperm chromatin in toroidal structures each embedding 50 to 100 kb of DNA. thus permitting the great decrease in nuclear volume (one tenth that of a somatic nucleus). At the end of spermatogenesis a fraction of the sperm chromatin is still in nucleosomal arrangement. Remaining histone-containing nucleosomes (folded histone solenoids) punctuate the toroidal chromatin structure. In addition, the small DNA linker strands going from one toroid to another are also associated with histones. At some points, these histone-associated strings of DNA are bound to the sperm nuclear matrix [63]. During post-testicular epididymal maturation of spermatozoa, the nucleus is further condensed by means of intense disulfide bridging. A nuclear located enzyme (sperm nucleus glutathione GPx4 = snGPx4) working as a disulfide isomerase uses luminal reactive oxygen species (ROS), essentially hydrogen peroxide (H₂O₂) to create inter- and intra-protamine disulfide bounds on thiol groups carried by the cysteine-rich protamines. It further condenses the sperm nucleus and locks it up in that condensed state [93].