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Fig. 1 | Basic and Clinical Andrology

Fig. 1

From: Mammalian sperm nuclear organization: resiliencies and vulnerabilities

Fig. 1

Schematic representation of the testicular and epididymal events leading to the drastic change in sperm chromatin organization. In testes, spermatogenesis permits to transform diploid spermatogonia into haploid spermatozoa. Spermatogenesis can be subdivided into three major steps: a mitotic amplification which ensures the proliferation and maintenance of spermatogonia, a meiotic step in which spermatogonia undergo to form spermatocytes which differentiate into spermatids and a post-meiotic step also known as spermiogenesis which makes spermatozoa. During spermiogenesis, the round spermatids undergo several morphological and biochemical modifications characterized by the acquisition of final nuclear shape and the replacement of somatic type histones by protamines. Histones that organize the DNA (146 bp) into nucleosomes are gradually replaced by testis-specific histone variants, and sudden post-translational modifications (for example hyperacetylation), followed by the replacement of most histones by at first by DNA interacting non histones, then by transitions proteins Tnp1 and Tnp2 and finally by protamines (Prms). Sperm DNA-protamine interaction leads in a unique appearance that involves the coiling of sperm DNA into toroidal subunits, also known as “doughnut loops”, that contain around 50 kb to 100 kb of DNA. At the end of spermatogenesis a fraction of the sperm chromatin is still in nucleosomal arrangement. Remaining histone-containing nucleosomes (folded histone solenoids) punctate the toroidal chromatin structure. In addition, the small linker DNA strands going from one toroid to another are also associated with histones. At some locations, these histone-associated strings of DNA are bound to the sperm nuclear matrix. During post-testicular epididymal maturation of spermatozoa, the nucleus is further condensed by means of intense disulfide bridging. A nuclear 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 a condensed state

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