title: Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males.
abstract: Phospholipid hydroperoxide glutathione peroxidase (PHGPx) was intensely expressed in mitochondria in the midpiece of human spermatozoa by immunostaining with anti-PHGPx monoclonal antibodies. The PHGPx not only reduced phospholipid hydroperoxide but also scavenged hydrogen peroxide in human spermatozoa. We found a dramatic decrease in the level of expression of PHGPx in the spermatozoa of some infertile males by immunoblotting with anti-PHGPx monoclonal antibodies. These individuals accounted for about 10% of the group of 73 infertile males that we examined. All seven patients with PHGPx-defective spermatozoa were classified as suffering from oligoasthenozoospermia, a defect in which both the number and the motility of spermatozoa are significantly below normal. Males with PHGPx-defective spermatozoa accounted for 26% of the 27 infertile males with oligoasthenozoospermia. No defects in expression of PHGPx in spermatozoa were observed in 31 fertile volunteers. After a 3-h incubation, the relative number of motile spermatozoa with low-level expression of PHGPx was significantly lower than that of spermatozoa with normal expression of PHGPx. The PHGPx-defective spermatozoa failed to incorporate rhodamine 123, revealing a loss of mitochondrial membrane potential. Ultrastructual analysis of mitochondria by electron microscopy demonstrated that the morphology of mitochondria in PHGPx-defective spermatozoa was abnormal. The results suggest that failure of the expression of mitochondrial PHGPx in spermatozoa might be one of the causes of oligoasthenozoospermia in infertile men.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Ishizaka
authors.forename: S
authors.initials: S
authors.lastname: Ichinose
authors.forename: H
authors.initials: H
authors.lastname: Oshima
authors.forename: I
authors.initials: I
authors.lastname: Okayasu
authors.forename: K
authors.initials: K
authors.lastname: Emoto
authors.forename: M
authors.initials: M
authors.lastname: Umeda
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
mesh_terms: D000911:Antibodies, Monoclonal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007248:Infertility, Male / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D009845:Oligospermia / Q000201:enzymology / Q000235:genetics; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D015347:RNA Probes; D012661:Semen / Q000201:enzymology; D013081:Sperm Motility / Q000235:genetics; D013094:Spermatozoa / Q000201:enzymology* / Q000648:ultrastructure; D013737:Testis / Q000201:enzymology
chemical_list: D000911:Antibodies, Monoclonal; D015347:RNA Probes; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase