- Title
- Apoptosis and DNA damage in human spermatozoa
- Creator
- Aitken, R. John; Koppers, Adam J.
- Relation
- Asian Journal of Andrology Vol. 13, Issue 1, p. 36-42
- Publisher Link
- http://dx.doi.org/10.1038/aja.2010.68
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2011
- Description
- 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.
- Subject
- apoptosis; DNA damage; oxidative stress; spermatatozoa
- Identifier
- http://hdl.handle.net/1959.13/1316598
- Identifier
- uon:23215
- Identifier
- ISSN:1008-682X
- Rights
- This work is licensed under the terms of Creative Commons Attribution-NonCommercial-Share Alike 3.0 license (CC BY-NC SA). The “Contribution” is defined as the text content of the paper named above and all supplementary information such as but not limited to tables, graphs and images. This licence allows readers to copy, distribute and transmit the Contribution as long as it is attributed back to the author. Readers are permitted to alter, transform or build upon the Contribution as long as the resulting work is then distributed under this or a similar licence. Readers are not permitted to use the Contribution for commercial purposes.
- Language
- eng
- Full Text
- Reviewed
- Hits: 2135
- Visitors: 2988
- Downloads: 768
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 268 KB | Adobe Acrobat PDF | View Details Download |