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.

Figure 1

Summary of the major causes of DNA damage due to intrinsic and extrinsic factors Reproduced and modified with permission from Menezo et al. [38].

Figure 2

Diagram of spermatogenesis initiated with the mitotic proliferation of spermatogonia (SSC; 2n) followed by first meiotic (I) division resulting in the formation of primary and secondary spermatocytes (SP). Through meiotic division (II), 2° SPs generate haploid round spermatids (RS) entering the differentiation process of spermiogenesis to produce elongating spermatids (ES) and mature sperm.

Figure 3

The canonical and NHEJ-alternative pathways. (A) The canonical NHEJ pathway, involving KU and XRCC4, can seal double-strand ends, even distal and non-fully complementary ends, in a conservative fashion; (B) In the alternative pathway, the main event is extended deletion at the junction, generally associated with the use of internal microhomologies distant from the ends. And XRCC1 and DNA ligase-III are used for strand ends ligation.