The Y chromosome is thought to be important for male reproduction. We have previously shown that with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrated that live mouse progeny can also be generated 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.
At present, our findings in mice do not translate directly to humans. ROSI is still considered experimental in human ART due to concerns regarding the safety of injecting immature germ cells and technical difficulties (23). In spite of this, some children have already been born (24, 25) and those were healthy. As we learn more about the effects and improve technical aspects of ROSI, this method may become more acceptable. Indeed, studies on ROSI effects in mice have been encouraging (26). Thus our study may bear importance for clinicians working in ART clinics supporting the possibility that ROSI may be a viable option for overcoming infertility in men with non-obstructive azoospermia.
Considering that we have obtained live offspring using germ cells from males with only two Y chromosome genes one could question the importance of Y chromosome in male reproduction. We believe that the answer lies in defining the need. Human Y chromosome is not on the way to oblivion, as it has been implied in the past (27), and its genetic information is undoubtedly important for many aspects of reproduction involving the development of mature sperm and its function in normal fertilization (28). Most of the mouse Y chromosome genes are involved in spermiogenesis and sperm function and as such are necessary for normal fertilization (29, 30). However, when it comes to assisted reproduction, 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 mouse Y chromosome altogether if appropriate replacements are made for those two genes.
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