Researchers hope the findings will be used to create treatment for men who cannot produce healthy sperm cells
The Y chromosome is thought to be important for male reproduction. A research group has recently shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Now, they demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y. Sry is believed to function primarily in sex determination during fetal life. Eif2s3y may be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.
"Only two Y-chromosome genes are needed to have children with the help of assisted reproduction," study author Monika Ward, a reproductive biologist at the University of Hawaii in Honolulu, told LiveScience. The scientists detailed their findings online today (Nov. 21, 2013) in the journal Science.
Past research showed that when a gene called Sry was inserted into mouse embryos that are genetically female, "it changed the fate of the mice," Ward said. "Even though they had two X chromosomes, they developed into males." These mice developed testicles and produced sperm precursor cells known as spermatogonia; however, these cells did not develop into sperm cells.
In the new work, the researchers added other Y-chromosome genes, one at a time, into such mice. The trial-and-error process eventually revealed a gene called Eif2s3y helped spermatogonia occasionally develop into spermatids, or immature sperm.
Spermatids are round cells, lacking the whiplike tails that mature sperm use to swim toward and fertilize egg cells. This means that although mice with Sry and Eif2s3y are male and can generate sex cells, they cannot normally have offspring.
To see if males with this pair of Y genes could reproduce with a little help, Ward and her colleagues injected these spermatids directly into egg cells. They found they could successfully fertilize the eggs with this method, resulting in viable offspring.
The researchers emphasized the whole Y chromosome is likely needed for normal reproduction — its other genes help mature sperm develop.
"We're not trying to eliminate Y chromosomes with our work — or men, for that matter," Ward explained. "We're just trying to understand how much of the Y chromosome is needed, and for what."