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Original

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

, &
Pages 3-10 | Received 17 Aug 2007, Accepted 23 Oct 2007, Published online: 09 Jul 2009
 

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

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