Of mice and men

时间:2019-03-08 09:15:00166网络整理admin

By Bob Holmes THE day when rodents routinely foster human sperm has come one step closer to reality. A scientist in Japan claims that he has used the testes of rats and mice for this purpose. The first fertilisations of human eggs from rodent-reared sperm could come within the next few weeks, he says. Growing the sperm of one species in the testes of another has been a serious possibility since 1996, when Ralph Brinster and his colleagues at the University of Pennsylvania in Philadelphia showed that sperm precursor cells, or spermatogonia, from rats could develop into mature sperm in the testis of a mouse. This led other researchers to suggest that human sperm might be cross-fostered in the same way (This Week, 31 January 1998, p 4). If so, the technique could offer hope of fatherhood for many infertile men. One researcher who took up the challenge was Nikolaos Sofikitis of Tottori University in Yonago, Japan. Sofikitis took spermatogonia from infertile men and injected them into the testes of rats and mice that had been specially bred to have defective immune systems. “For three years, I failed,” he says. Finally, Sofikitis hit on the secret. Along with the human spermatogonia, he injected cells from the recipient rodent’s eye. These cells—from the fluid just in front of the lens—secrete a protein called fas ligand, a signalling molecule that triggers immune cells to commit suicide. This eliminated the last vestiges of an immune response and allowed the spermatogonia to take, Sofikitis says. Sofikitis gave the injections to 10 rats and 8 mice. Five months later, he detected large numbers of mature human sperm in three rats and two mice. In one rat, he found fully motile sperm “with better motility than that of many fertile men”. Other scientists remain sceptical, noting that Sofikitis’s work has not yet passed peer review. However, all agree that such an achievement would be a major advance. “If this guy’s done it, it’s great. We haven’t been able to get past first base,” says Roger Short, a reproductive biologist at the Royal Women’s Hospital in Melbourne. If Sofikitis’s technique holds up, it would give researchers a powerful new tool because they could study the development of human sperm in animals instead of humans, says Short. That could speed up the development of male contraceptive drugs that prevent sperm from maturing. Fostered sperm could also allow infertile men who cannot produce sperm to father children through IVF. Sofikitis has fertilised hamster eggs with hamster sperm fostered in rat testes, and he expects the same should be possible for people. However, no one knows yet whether such sperm might run a higher risk of being genetically damaged. The sperm could also carry disease if they become contaminated with rodent viruses, says Dolores Lamb, an andrologist at Baylor College of Medicine in Houston, Texas. Because of these doubts, experts are cautious about human tests. “You’d sure want to see it work in nonhuman primates first,” says Arnold Belker, a urologist at the University of Louisville in Kentucky. Nonetheless, Sofikitis has applied to the Japanese government for permission to proceed in humans, and hopes to fertilise human eggs with fostered sperm within a few weeks, allowing the embryos to develop for no more than 6 days. “There are ethical barriers,