Researchers have described their effort to identify the minimum Y chromosome contribution required to generate a healthy first generation mouse, capable of reproducing a second generation on its own without further technological intervention.
The Y chromosome is a symbol of maleness, present only in males and encoding genes important for male reproduction. But live mouse offspring can be generated with assisted reproduction 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.
Advertisement"Does this mean that the Y chromosome (or most of it) is no longer needed? Yes, given our current technological advances in assisted reproductive technologies," said Monika A. Ward, Associate Professor at the Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawai.
At the same time, however, she also emphasized the importance of the Y chromosome for normal, unassisted fertilization and other aspects of male reproduction.
Ward and her colleagues used transgenic male mice with only two Y genes, Sry and Eif2s3y. The mice were considered infertile because they had meiotic and postmeiotic arrests- that is, the germ cells that should have normally developed into sperm did not fully mature in these mice- but researchers were able to find few usable cells.
Yasuhiro Yamauchi, a post-doctoral scholar on Ward's team, harvested these immature spermatids and used a technique called round spermatid injection (ROSI) to successfully fertilize oocytes in the laboratory. When the developed embryos were transferred to female mouse surrogate mothers, live offspring were obtained.
Because the overall efficiency of ROSI with two Y genes was lower than with regular, fertile mice, the researchers then looked to see whether the addition of other Y genes could improve it. They increased the live offspring rate by about two-fold when Sry was replaced with the sex reversal factor Sxrb, which encodes three additional Y genes.
These results demonstrated that Sxrb encodes a gene or genes that enhance the progression of spermatogenesis.
The study's findings are relevant but not directly translatable to human male infertility cases. In the era of assisted reproduction technologies, it is now possible to bypass several steps of normal human fertilization using immotile, non-viable, or immature sperm.
Ward said that most of the mouse Y chromosome genes are necessary for normal fertilization. However, when it comes to assisted reproduction, the 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.
The study is published in the journal Science.