A new study has promising results for those battling male infertility.
Researchers at the John A. Burns School of Medicine, University of Hawaii have shown that male mice with only two genes from the Y chromosome can successfully produce offspring. The same team previously demonstrated that only seven genes from the Y chromosome were necessary, which means that researchers are getting closer to breeding mice without any contribution from the Y -- or male -- chromosome at all.
As the BBC reported it, "Scientists have practically obliterated the ultimate symbol of maleness in DNA, the Y chromosome, and believe they may be able to do away with it completely."
The study started off by genetically engineering male mice to lack the Y chromosome, thus making them entirely infertile. Researchers then made the mice "male" again by adding back two genes (Sry and Eif2s3y) for sperm production: one that would make them grow testes and one that would cause the testes to produce sperm.
And it worked -- kind of. The mice had smaller testes and produced fewer, less developed sperm, but researchers were able to find enough viable sperm for use in an in vitro fertilization (IVF) technique called round spermatid injection (ROSI). The success rate of the ROSI procedures was lower than with regular, fertile mice (9% compared to 26%), but the resulting offspring were healthy and even fertile themselves.
According to Jennifer Marshall Graves, a geneticist at the La Trobe Institute of Molecular Science in Melbourne, Australia, who was not involved in the research, "it is a further demonstration that there isn't much left on the poor old Y chromosome that is essential. Who needs a Y?”
While this is alarming news for most men, it is promising news for men dealing with infertility. A common cause of male infertility is a defective Y chromosome or the inability to produce fully formed sperm for another reason. Fertility specialists fear that using IVF techniques like ROSI to implant such immature sperm in human embryos would contribute to genetically defective offspring.
The University of Hawaii study may alleviate some of those fears. Lead researcher Professor Monika Ward told the BBC that "on a practical level [the study] shows that after large deletions of the Y chromosome it is still possible to reproduce, which potentially gives hope to men with these large deletions."
The researchers were careful to note, however, that “Our findings are relevant, but not directly translatable, to human males." The genes involved in the production of healthy sperm in men, after all, are not identical to those studied in the mice.
“Most of the mouse Y chromosome genes are necessary for normal fertilization,” Ward said in Kaunana, a University of Hawaii publication. “However, when it comes to assisted reproduction, our mouse study proves that the Y chromosome contribution can be brought to a bare minimum. It may be possible to eliminate the mouse Y chromosome altogether if appropriate replacements are made for those two genes.”
By that, Ward means activating partner genes on other chromosomes to make up for the two necessary Y chromosome genes, thus eliminating their involvement entirely.
Sound like science fiction? Maybe, but as Dr. Chris Tyler-Smith, from the Wellcome Trust Sanger Institute, told the BBC, "This is a great step forward in understanding basic biology."
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