| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
It has been suggested that damaged genomic DNA of the spermatozoa in patients with male infertility can be transmitted to the progeny, and may inhibit embryonal development. Recent our studies have demonstrated that a high level of oxidative stress causes DNA damages of the spermatozoa, and such stress induce apoptotic loss of testicular germ cells. In this study, we investigated the mechanism of DNA damage and apoptosis in the testicular germ cells, and investigate the apoptotic signals of early human and rat embryos. The results obtained are as follows.
1. Heat shock protein 105 (HSP105) is specifically localized in the germ cells, and may translocate into the nucleus after heat shock. HSP105 is suggested to form a complex with p53 at scrotal temperature, and dissociate from it at suprascrotal temperature.
2. In the surgically induced cryptorchidism in immature rats, xanthine oxidase inhibitors attenuated weight reduction of the cryptorchid testis and apoptotic loss of germ cells. In cultured testicular cells, treatment with xanthine oxidase inhibitors prevented DNA cleavage into low molecular weight ladders characteristic of apoptosis.
3. In rat embryos, Fas mRNA was expressed at 2-cell stage only, whereas Fas ligand (Fas L) mRNA was expressed at oocytes, pronuclear (1-cell) and 2-cell stages. In human embryos, Fas mRNA was expressed at the 4-cell stage only, whereas Fas L mRNA was expressed at both 2-and 4-cell stages.
In conclusions, 1)HSP105 may contribution to stabilization of p53 proteins in the cytoplasm in the germ cells at scrotal temperature, 2)Xanthine oxidase inhibitors inhibit apoptotic death of germ cell induced by heat stress, and 3) Simultaneous expression of Fas and Fas L mRNAs at 2-cell embryos in rats and 4-cell embryos in human may be associated with apoptosis of the early embryos.
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