August 18, 2009

An Antioxidant Enzyme That Protects Spermatozoa

GPx5, an antioxidant protein that protects immature spermatozoa once they have left the testicle, has been identified by the GReD Unit (1) (CNRS / INSERM / Universities de Clermont-Ferrand).  This discovery by Joël Drevet and his team establishes a link between post-testicular oxidative stress and degradation of the DNA in male gametes.  These findings, which presage a major clinical impact "“ particularly in the context of medically-assisted procreation (MAP) "“ have been published in the Journal of Clinical Investigation (JCI).

Spermatozoa form in the testicles and then leave to mature in the epididymis, where they acquire their fertilizing capacities.  During these maturation stages, vulnerable spermatozoa are subjected to oxidative stress that can damage membrane lipids or even DNA.  To prevent this oxidative damage during their maturation and storage between two ejaculations, the gametes are partially protected by GPx5 (2), an antioxidant enzyme secreted by the epididymal epithelium.

This study showed that male mice devoid of this protein produced spermatozoa that were morphologically normal and wholly capable of fertilizing an oocyte.  However, when wild-type females were crossed with the same GPx5-deficient males, abnormally elevated levels of developmental defects, and an increase in the number of abortions and perinatal mortality were observed.  The causes were elucidated by in-depth analyses of spermatozoa from GPx5-devoid animals, which revealed oxidative damage to sperm DNA, which was compacted and tended to fragment.  

In a commentary on this article, John Aitken from the University of Newcastle (Australia) pointed out that these results could have a major clinical impact in the context of the fertility of aging men and MAP technologies.  

If these findings are confirmed in humans, several applications could be envisaged in the diagnosis and correction of post-testicular infertility.  In the field of medically-assisted procreation, these results would enable the protection of sperm (3) during thawing prior to artificial insemination, and more generally provide a clearer understanding of the fragmentation of sperm DNA in the context of MAP technologies.


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