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. 鈥淔or three years, I failed,鈥� he says.
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Finally, Sofikitis hit on the secret. Along with the human spermatogonia, he
injected cells from the recipient rodent鈥檚 eye. These cells鈥攆rom the fluid
just in front of the lens鈥攕ecrete 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 鈥渨ith better motility than that of many fertile
尘别苍鈥�.
Other scientists remain sceptical, noting that Sofikitis鈥檚 work has not yet
passed peer review. However, all agree that such an achievement would be a major
advance. 鈥淚f this guy鈥檚 done it, it鈥檚 great. We haven鈥檛 been able to get past
first base,鈥� says Roger Short, a reproductive biologist at the Royal Women鈥檚
Hospital in Melbourne.
If Sofikitis鈥檚 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. 鈥淵ou鈥檇 sure
want to see it work in nonhuman primates first,鈥� 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.
鈥淭here are ethical barriers,鈥� he admits. 鈥淏ut in medicine if you want to do
something new you always have ethical barriers to overcome.鈥�