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Abstract
To review the mechanisms responsible for DNA fragmentation in human sperm, including
those occurring during spermatogenesis and transport through the reproductive tract.
The mechanisms examined include: apoptosis in the seminiferous tubule epithelium,
defects in chromatin remodeling during the process of spermiogenesis, oxygen radical-induced
DNA damage during sperm migration from the seminiferous tubules to the epididymis,
the activation of sperm caspases and endonucleases, damage induced by chemotherapy
and radiotherapy, and the effect of environmental toxicants. The different tests currently
used for sperm DNA fragmentation analysis and the factors that determine the predictive
value of sperm DNA fragmentation testing and their implications in the diagnosis and
treatment of infertility are also discussed. Finally, we also scrutinize how the presence
in the embryonic genome of DNA strand breaks or modifications of DNA nucleotides inherited
from the paternal genome could impact the embryo and offspring. In particular we discuss
how abnormal sperm could be dealt with by the oocyte and how sperm DNA abnormalities,
which have not been satisfactorily repaired by the oocyte after fertilization, may
interfere with normal embryo and fetal development.
Sperm DNA can be modified through various mechanisms. The integrity of the paternal
genome is therefore of paramount importance in the initiation and maintenance of a
viable pregnancy both in a natural conception and in assisted reproduction. The need
to diagnose sperm at a nuclear level is an area that needs further understanding so
that we can improve treatment of the infertile couple.
Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc.
All rights reserved.