Male infertility linked to an enzyme complex issue

By Sally Robertson, B.Sc.Oct 15 2012

An enzyme complex present in sperm plasma membranes plays an important role in the overproduction of reactive oxygen species (ROS) and oxidative stress in sperm with abnormal morphology, researchers have shown.

They report that levels of nicotinamide adenine dinucleotide phosphate-oxidase 5 (NOX5) were significantly higher in teratozoospermic semen compared with normozoospermic semen in an analysis of samples from 25 individuals attending an infertility center at Shiraz University of Medical Sciences in Iran.

"To the best of our knowledge, this study is the first to demonstrate differentially higher expression of NOX5 in teratozoospermic semen samples," say Sara Keshtgar and colleagues.

Oxidative stress from excessive ROS generation is a major cause of male infertility, and NOX5 has recently been implicated in ROS generation in sperm, based on its location in the flagella/neck region and the acrosome of mature human spermatozoa, and its stimulatory effect on superoxide production in response to calcium elevation, explain the researchers.

As teratozoospermic semen samples produce higher levels of ROS compared with normozoospermic samples, the team examined whether there was a differential existence and density of NOX5 between the semen types.

As reported in Andrologia, the team divided the semen samples into normozoospermic (n=12) and teratozoospermic (n=13) groups, according to a cutoff of less than 40% of sperm with normal morphology.

Flow cytometry demonstrated the expression of NOX5 in acrosomal, equatorial, postacrosomal regions, the body, and the tail of both normal and abnormal sperm.

Furthermore, it revealed that cumulative percentages of NOX5-expressing spermatozoa were significantly higher in the teratozoospermic group than in the normozoospermic group, at 86.9% versus 65.7%. Moreover, the mean fluorescent intensity of stained cells was significantly higher in teratozoospermic samples than in normozoospermic samples, indicating higher expression levels.

In addition, abnormal sperm morphology correlated positively with the percentage of NOX5-positive sperm and the intensity of NOX5 expression.

"This may be due to the large amount of excess cytoplasm in some abnormal sperm," suggest Keshtgar et al.

The researchers say a positive correlation between ROS generation in teratozoospermia and that in NOX5 expression can be assumed based on the findings.

"However, more studies on enzymatic activity of NOX5 and evaluation of ROS generation by this enzyme in sperm cells should be carried out," they conclude.

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