Abstract
During the haploid phase of spermatogenesis, spermatids undergo a complex remodeling of the paternal genome involving the finely orchestrated replacement of histones by the highly-basic protamines. The associated striking change in DNA topology is characterized by a transient surge of both single- and double-stranded DNA breaks in the whole population of spermatids which are repaired before spermiation. These transient DNA breaks are now considered part of the normal differentiation program of these cells. Despite an increasing interest in the study of spermiogenesis in the last decade and the potential threat to the haploid genome, the origin of these DNA breaks still remains elusive. This review briefly outlines the current hypotheses regarding possible mechanisms that may lead to such transient DNA fragmentation including torsional stress, enzyme-induced breaks, apoptosis-like processes or oxidative stress. A better understanding of the origin of these DNA breaks will lead to further investigations on the genetic instability and mutagenic potential induced by the chromatin remodeling.
Highlights
In addition to the reduction of their chromosome number, post meiotic haploid cells undergo one of the most drastic changes in nuclear organization known to the eukaryotic domain
Proper compaction is essential for fertilization and embryogenesis [2] and alteration in the sperm chromatin state is linked to impaired spermatogenesis and infertility [3,4]
From studies using histone deacetylases inhibitors, induced hyperacetylation of histones in cultured cells leads to a greater vulnerability to DNA damage and DNA double-strand breaks (DSBs) are observed [11,12]
Summary
In addition to the reduction of their chromosome number, post meiotic haploid cells (spermatids) undergo one of the most drastic changes in nuclear organization known to the eukaryotic domain. Increase of poly (ADP-ribosyl)ation at break sites might cause early release of TOP2B, since it has lost its ability to bind DNA due to its interaction with the highly negatively charged polymer [36] According to this observation, one may surmise that DSBs could be a direct result of an abortive TOP2B catalytic cycle during chromatin remodeling in elongating spermatids. Round spermatid expression data indicate that SPO11 transcripts are present to a much higher level than those of TOP2B during early spermiogenesis [39] This warrants further investigation regarding the expression and the functional role of the SPO11 proteins in the formation of chromatin remodeling DSBs. Apoptosis-like pathway Terminal differentiation of vertebrate cells, including lens fiber cells and erythrocytes appears molecularly and biochemically related to apoptosis [40]. The quantification of 8-oxo guanine, used as a reliable oxidative stress marker [62], during the spermatid’s chromatin remodeling steps could be an interesting way to investigate the implication of ROS at these stages
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
