Types, Causes, Detection and Repair of DNA Fragmentation in Animal and Human Sperm Cells

Abstract

Concentration, motility and morphology are parameters commonly used to determine the fertilization potential of an ejaculate. These parameters give a general view on the quality of sperm but do not provide information about one of the most important components of the reproductive outcome: DNA. Either single or double DNA strand breaks can set the difference between fertile and infertile males. Sperm DNA fragmentation can be caused by intrinsic factors like abortive apoptosis, deficiencies in recombination, protamine imbalances or oxidative stress. Damage can also occur due to extrinsic factors such as storage temperatures, extenders, handling conditions, time after ejaculation, infections and reaction to medicines or post-testicular oxidative stress, among others. Two singular characteristics differentiate sperm from somatic cells: Protamination and absence of DNA repair. DNA repair in sperm is terminated as transcription and translation stops post-spermiogenesis, so these cells have no mechanism to repair the damage occurred during their transit through the epididymis and post-ejaculation. Oocytes and early embryos have been shown to repair sperm DNA damage, so the effect of sperm DNA fragmentation depends on the combined effects of sperm chromatin damage and the capacity of the oocyte to repair it. In this contribution we review some of these issues.

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

“…The latter can be further supported by the fact that Fas may be found externalized to the membrane of mature sperm in the ejaculate [7,25]. These mechanisms will ultimately alter the sperm proteome through: (i) error in the translation of fragmented genes, because the sperm transcription and translation processes will become quiescent only after spermiogenesis [24], and (ii) different protein exchange between the sperm membrane and the epididymal fluid during sperm storage, maturation, and traffic. In normal conditions, the epididymal fluid and the sperm membrane undergo intense protein exchanges, including the removal of specific testicular proteins from the membrane and the addition of secreted epididymal proteins [26].…”

“…Under this rationale, even a viable subset from an ejaculate with a higher amount of sperm with DNA fragmentation is expected to contain proteomics alterations, because (i) oxidative DNA damage, which is responsible for the oxidation of sperm membrane proteins, can occur during the entire male reproductive process, i.e. during spermatogenesis, epididymal maturation, sperm transit or even after ejaculation [24], and (ii) the ejaculation of a subset of sperm which had its DNA fragmented in the testis might reveal a dysfunction in the selection mechanisms by Sertoli cells, suggesting that viable sperm with an altered proteome can also be ejaculated. The latter can be further supported by the fact that Fas may be found externalized to the membrane of mature sperm in the ejaculate [7,25].…”

A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation

“…B 283: 20152708 sections of the female reproductive tract. Another untested hypothesis is that the repair of DNA fragmentation that happens within the fertilized oocyte [45] may be more efficient or increased in species with high levels of sperm competition, leading to a coevolutionary process that may compensate for high levels of sperm DNA damage in such species. The higher prevalence of sperm DNA fragmentation in species with high levels of sperm competition could be due to higher levels of oxidative stress in these species.…”

Paternal contribution to development: Sperm genetic damage and repair in fish

“…Therefore, defective BER activity results in an increase in double-strand breaks after replication (Hilton et al 2013;Metzger et al 2013), one of the most detrimental lesions that can lead to genomic instability and cell death (González-Marín et al 2012). Double strand breaks can, in turn, be repaired by non-homologous recombination end joining (NHEJ) pathway, which increases the genetic instability, or homologues recombination (HR) pathway (Derijck et al 2008).…”