Failure of phospholipid hydroperoxide glutathione peroxidase expression in oligoasthenozoospermia and mutations in the PHGPx gene.
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a selenoprotein belonging to the family of glutathione peroxidases. PHGPx has long been considered a major antioxidant that, in cooperation with vitamin E, protects biomembranes. To determine the expression pattern of PHGPx mRNA in human, quantitative RT-polymerase chain reaction (PCR) analyses using RNA from different embryonal and adult tissues were performed. A predominant expression was found in testes. In spermatozoa, PHGPx was found to be localized in the mid-piece of spermatozoa. We studied the relationship between spermatozoa PHGPx expression, mutations in PHGPx gene and human oligoasthenozoospermia, a defect in which both the number and the motility of spermatozoa are significantly below normal. Spermatozoa specimens from 45 infertile males were analysed for fertility-related parameters according to World Health Organisation and were classified as suffering from oligoasthenozoospermia. Two patients (4.44%) showed no expression of PHGPx and in nine patients (20.00%), a reduced expression of the enzyme was observed. DNA sequences of various regions of the PHGPx gene (coding, 5'flanking region and intron 1) from these patients and 58 fertile volunteers were analysed for mutations by PCR amplification and direct sequencing. Sequence data revealed no cause/effect relationship for any of the variants. From these data it can be concluded that oligoasthenozoospermia is associated with a decrease in the level of expression of PHGPx in the spermatozoa of some infertile men (24.44%), but is not linked to mutations in PHGPx gene.
Diaconu
M
M
Institute of Human Genetics, University of Göttingen, Germany.
Tangat
Y
Y
Böhm
D
D
Kühn
H
H
Michelmann
H W
HW
Schreiber
G
G
Haidl
G
G
Glander
H-J
HJ
Engel
W
W
Nayernia
K
K
D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics; D008297:Male; D009154:Mutation; D009845:Oligospermia / Q000201:enzymology* / Q000235:genetics*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013081:Sperm Motility
D012313:RNA; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase