Molecular mechanism of apoptosis of reproductive cells and fertilization

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1) To understand the molecular mechanisms leading to ovarian follicular atresia in MRL/lpr mouse, we examined the apoptotic signalling pathway. The results indicated that MRL/+ murine oocytes and MRL/lpr is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL/lpr murine oocytes caused by insertion of the early transposable element into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.2) Six apoptosis-inducing nucleosides (AINs) released into cell culture media of 57.DR-NS (the CD57^+HLA-DR-<bright> natural suppressor cell line deri … More ved from human decidual tissue) were isolated by the combination of physicochemical procedures. Subsequently, we demonstrated that AINs could induce apoptosis 'in human leukemia Molt4 and carcinoma BeWo/GCIY cells but not human fibroblast WI-38 cells. The AINs also induced apoptosis in human prostate cancer PC3 cells, estrogen-non-responsive human breast carcinoma MDA-MB-435 cells, and human gastric carcinoma cells. Apoptosis was characterized by DNA strand breaks and activation of the caspase cascade, especially caspase-3. The administration of AINs into tumor bearing SCID mice culminated in suppression of tumor growth due to apoptosis of tumor cells.3) By using sugar probes, we found several proteins in boar sperm lysate which bind to oligosaccharide probes. One of them was a homologue of ADAM4 based on the analysis of partial amino acid sequence. We cloned its cDNA, and produced its recombinant protein in a secreted form in yeast. Functional analysis indicated that the protein has an adhesion activity to integrin, suggesting its role in fertilization. Less