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Suicide mission - Understanding how sperm kill themselves could lead to a male pill

点击量:   时间:2017-12-17 07:01:01

By Philip Cohen ABNORMAL sperm turn suicidal in order to prevent harmful mutations being passed to offspring, a new report says. Every day, the average human male churns out about 200 million new sperm. With such huge quantities being produced, biologists have wondered what steps are taken to ensure quality. Paul Burgoyne of the National Institute for Medical Research in London thought that one obvious place for a quality check on sperm is during meiosis—cell divisions in which daughter cells have only one of each chromosome pair. During these divisions, the maternal copy of each chromosome pairs off at the centre of the cell with its paternal double. The only odd couple is formed when the maternal X chromosome pairs off with the paternal Y chromosome. Once doubled up, the pairs separate, each ending up in a different sperm cell. This way, each sperm has half the original number of chromosomes and can fuse with an egg to create an embryo. If, by accident, a chromosome fails to pair up, it and its partner risk ending up in the same sperm cell. An embryo formed from that sperm would have too many chromosomes and either die or suffer abnormalities. To test whether there was any mechanism to stop this happening, Burgoyne and his colleagues engineered a mouse strain in which the males carried an X and a Y chromosome that were fused together. The researchers found that the faulty sperm stalled the assembly line at the point of pairing, and that they rested there twelve times more often than the normal sperm. The researchers also found that the chromosomes in the sperm cells, which are normally millions of DNA bases long, had been chewed down to pieces hundreds of bases long (Nature Genetics, vol 18, p 257). This shredding is a hallmark of a form of cellular suicide called apoptosis. Burgoyne’s team suspected that a protein called p53 triggers the cell suicide. When breaks occur in chromosomes of ordinary, non-reproductive cells, p53 helps recognise the damage and forces the cells to kill themselves. Yet when the team knocked out the p53 gene in their mice, the sperm with fused XY chromosomes were just as likely to take their own lives. Burgoyne suggests sperm evolved a more specific technique for destroying mistakes. “If they relied on p53, too many healthy cells would get knocked on the head,” he says. His team hopes to discover which gene plays the grim reaper in sperm. Robert Braun of the University of Washington in Seattle says the study has some interesting implications. “If you could induce this suicide with a drug, then you might have a powerful male contraceptive,