Apoptosis and DNA damage in human spermatozoa

R Aitken, Adam Koppers

Research output: Contribution to journalArticleResearchpeer-review

173 Citations (Scopus)

Abstract

DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.
Original languageEnglish
Pages (from-to)36 - 42
Number of pages7
JournalAsian Journal of Andrology
Volume13
Issue number1
DOIs
Publication statusPublished - 2011

Cite this

Aitken, R ; Koppers, Adam. / Apoptosis and DNA damage in human spermatozoa. In: Asian Journal of Andrology. 2011 ; Vol. 13, No. 1. pp. 36 - 42.
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Apoptosis and DNA damage in human spermatozoa. / Aitken, R; Koppers, Adam.

In: Asian Journal of Andrology, Vol. 13, No. 1, 2011, p. 36 - 42.

Research output: Contribution to journalArticleResearchpeer-review

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