Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) was intensely exp ressed in mitochondria in the midpiece of human spermatozoa by immunostaini ng with anti-PHGPx monoclonal antibodies. The PHGPx not only reduced phosph olipid hydroperoxide but also scavenged hydrogen peroxide in human spermato zoa. We found a dramatic decrease in the level of expression of PHGPx in th e spermatozoa of some infertile males by immunoblotting with anti-PHGPx mon oclonal antibodies. These individuals accounted for about 10% of the group of 73 infertile males that we examined. All seven patients with PHGPx-defec tive spermatozoa were classified as suffering from oligoasthenozoospermia, a defect in which both the number and the motility of spermatozoa are signi ficantly below normal. Males with PHGPx-defective spermatozoa accounted for 26% of the 27 infertile males with oligoasthenozoospermia. No defects in e xpression of PHGPx in spermatozoa were observed in 31 fertile volunteers. A fter a 3-h incubation, the relative number of motile spermatozoa with low-l evel expression of PHGPx was significantly lower than that of spermatozoa w ith normal expression of PHGPx. The PHGPx-defective spermatozoa failed to i ncorporate rhodamine 123, revealing a loss of mitochondrial membrane potent ial. Ultrastructual analysis of mitochondria by electron microscopy demonst rated that the morphology of mitochondria in PHGPx-defective spermatozoa wa s abnormal. The results suggest that failure of the expression of mitochond rial PHGPx in spermatozoa might be one of the causes of oligoasthenozoosper mia in infertile men.