The Y chromosome encodes genes important for natural male reproduction, but when it comes to assisted reproductive technologies, not all of those genes may be necessary to produce viable offspring. In fact, a new study shows that only two Y chromosome genes are needed to generate live mouse offspring with assisted reproduction: Sry, a gene critical for the development of testes, and Eif2s3y, which is needed to initiate spermatogenesis (Science published online 21 November 2013; doi:10.1126/science.1242544).

Monika Ward and her colleagues at University of Hawaii, Honolulu, previously demonstrated that, with the use of assisted reproduction, live offspring could be obtained from mice lacking the entire Y chromosome long arm; the remaining Y chromosome in these mice only encoded seven genes and three gene families. But now the team has further narrowed down the essential Y contribution to two genes, Sry and Eif2s3y.

The transgenic male mice with only these two Y genes were considered infertile because the germ cells that normally develop into sperm did not fully mature in these mice, instead remaining as round spermatids. The team harvested these immature, often abnormally shaped spermatids and used a technique called round spermatid injection (ROSI) to inject them into healthy female mouse eggs. When the successfully fertilized oocytes were transplanted into the oviducts of recipient females, live offspring were obtained. Furthermore, these offspring were capable of breeding.

“When it comes to assisted reproduction,” the authors wrote, “our mouse study proves that the Y chromosome contribution can be brought to a bare minimum consisting of Sry and Eif2s3y. Indeed, it may well be possible to eliminate the mouse Y chromosome altogether if appropriate replacements are made for those two genes.”

Credit: Sebastian Kaulitzki/Alamy

That is not to say that the remaining genes on the Y chromosome do not serve important functions in male fertility. The overall efficiency of ROSI with two Y genes was only 9%, much lower than the 26% success rate of ROSI with spermatids from normal XY males. When the researchers replaced Sry with the sex reversal factor Sxrb, which encodes three additional Y genes, as well as a partial chromosome to pair with the partnerless X chromosome during cell division, they were able to achieve ROSI success rates as high as 20%. As the authors explained, “Human Y chromosome...genetic information is undoubtedly important for many aspects of reproduction involving the development of mature sperm and its function in normal fertilization.”