ABSTRACT
Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674-683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermatocyte-specific GPx4 knock-out mice using a Cre-loxP system. All the spermatocyte-specific GPx4 knock-out male mice were found to be infertile despite normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. Isolated epididymal GPx4-null spermatozoa could not fertilize oocytes in vitro. 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 the depletion of GPx4 in spermatocytes causes severe abnormalities in spermatozoa. This may be one of the causes of male infertility in mice and humans.
Subject(s)
Glutathione Peroxidase/metabolism , Infertility, Male/enzymology , Spermatocytes/enzymology , Animals , Epididymis/metabolism , Female , Fertilization in Vitro , Male , Membrane Potentials , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase , Reactive Oxygen Species , Time FactorsABSTRACT
A 71-year-old previously healthy woman, presented with respiratory failure several days after initiation of cough and fever. A chest X-ray revealed multiple infiltrative shadows with airbronchograms in bilateral middle and lower lung fields. Transbronchial lung biopsy, performed after steroid pulse therapy which induced transient improvement, demonstrated exudative lesions with massive aggregation of histiocytes containing yeast-like fungi in their cytoplasm. Since the test for cryptococcal antigens was positive, a diagnosis of primary pulmonary cryptococcosis was made. Despite intravenous fluconazole injection for aweek, the severity of fungus infiltration increased. The treatment was therefore changed to a combination of intravenous amphotericin B and oral prednisolone, which achieved clinical improvement. In conclusion, in the case of rapidly progressive pulmonary cryptococcosis with widespread exudative lesions, addition of steroid therapy should be considered when antifungal agents alone prove ineffective.
Subject(s)
Cryptococcosis/complications , Lung Diseases, Fungal/complications , Respiratory Insufficiency/etiology , Acute Disease , Aged , Cryptococcosis/drug therapy , Female , Humans , Lung Diseases, Fungal/drug therapyABSTRACT
A 58-year-old man who had been prescribed corticosteroids for rheumatoid arthritis in another hospital was admitted to our hospital for examination of an abnormal chest shadow. We obtained a positive result for cryptococcal antigen in the serum, in a measurement done as a screening test for abnormal chest shadows. We diagnosed secondary pulmonary cryptococcosis through a transbronchial biopsy. He showed various radiographic changes, including multiple nodular shadows, cavities and partial resolution during the natural course without antifungal treatment. This case taught us that secondary pulmonary cryptococcosis causes a more varied range of radiographic changes than its primary form, that measurement of cryptococcal antigen in serum is useful as a screening test of pulmonary cryptococcosis, and that it is important to consider whether a particular patient should be treated or not.
