Abstract
Phospholipid hydroperoxide glutathione peroxidase(PHGPx) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. PHGPx is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of PHGPx in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia. To clarify whether defective PHGPx in testis causes male infertility, we established testis-specific PHGPx knockout mice using a Cre-loxP system. All the testis-specific PHGPx knockout male mice were found to be infertile in spite of normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. These spermatozoa showed significant reductions of forward motility and the mitochondrial membrane potential. These impairments were accompanied by the structural abnormality, such as a hairpin-like flagella bend at the midpiece and swelling of mitochondria in the spermatozoa. These results demonstrate that depletion of PHGPx in spermatozoa causes severe abnormalities in the spermatozoa, which may be one of the causes of male infertility in mice and humans.
