Abstract
This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.
Abbreviations | ||
AcH4 | = | Hyperacetylated histone H4 |
ART | = | Assisted reproduction technology |
SCSA | = | sperm chromatin structure assay |
BER | = | Base excision repair |
DDR | = | DNA damage response |
DSB | = | Double-strand breaks |
ES | = | Elongating spermatid |
ICSI | = | Intracytoplasmic sperm injection |
MMR | = | Mismatch repair |
NHEJ | = | Non-homologous end joining |
ROS | = | Reactive oxygen species |
SCSA | = | Sperm chromatin structure assay |
TDP1 | = | Tyrosyl-DNA phosphodiesterase 1 |
TP | = | Transition protein |
TUNEL | = | Terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling |
HR | = | homologous recombination |
TOP2B | = | topoIIβ: topoisomerase IIβ |
Abbreviations | ||
AcH4 | = | Hyperacetylated histone H4 |
ART | = | Assisted reproduction technology |
SCSA | = | sperm chromatin structure assay |
BER | = | Base excision repair |
DDR | = | DNA damage response |
DSB | = | Double-strand breaks |
ES | = | Elongating spermatid |
ICSI | = | Intracytoplasmic sperm injection |
MMR | = | Mismatch repair |
NHEJ | = | Non-homologous end joining |
ROS | = | Reactive oxygen species |
SCSA | = | Sperm chromatin structure assay |
TDP1 | = | Tyrosyl-DNA phosphodiesterase 1 |
TP | = | Transition protein |
TUNEL | = | Terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling |
HR | = | homologous recombination |
TOP2B | = | topoIIβ: topoisomerase IIβ |