The Y chromosome is a symbol of maleness, present only in males and encoding genes important for male reproduction. But a new study has shown that live mouse progeny can be generated with assisted reproduction using germ cells from males which do not have any Y chromosome genes. This discovery adds a new light to discussions on Y chromosome gene function and evolution. It supports the hypothesis that Y chromosome genes can be replaced by that encoded on other chromosomes.
Two years ago, the University of Hawaiʻi at Mānoa team led by Monika A. Ward, professor at the Institute for Biogenesis Research, John A. Burns School of Medicine, demonstrated that only two genes of the Y chromosome, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y, were needed for male mice to sire offspring with assisted fertilization. Now, the same team, with a collaborating researcher from France, Michael Mitchell from INSERM, Marseille, took an additional step and produced males completely devoid of the entire Y chromosome.
In this new study, scheduled for online publication in the journal Science on January 29, 2016, Ward and her UH colleagues describe how they generated the “No Y” males and define the ability of these males to produce gametes and sire offspring.
Shedding new light on Y chromosome gene function and evolution
“Most of the mouse Y chromosome genes are necessary for development of mature sperm and normal fertilization, both in mice and in humans,” Ward said. “However, when it comes to assisted reproduction, we have now shown that in the mouse the Y chromosome contribution is not necessary.”
The study provides new important insights into Y chromosome gene function and evolution. It supports the existence of functional redundancy between the Y chromosome genes and their homologues encoded on other chromosomes. “This is good news,” Ward said, “because it suggests that there are back-up strategies within genomes, which are normally silent but are capable of taking over under certain circumstances. We revealed two of these strategies by genome manipulation. Whether such alternative pathways would ever be activated without human help, for example in response to environmental changes, is unknown. But it is certainly possible and has already happened for two rodent species which lost their Y chromosomes.”
The development of assisted reproduction technologies (ART) allows bypassing various steps of normal fertilization by using immotile, non-viable, or immature gametes. The newest study as well as Ward’s preceding report (Science 2014 Jan 3;343(6166):69-72) support that in the mouse ROSI is a successful and efficient form or ART. In humans, ROSI is considered experimental due to concerns regarding the safety of injecting immature germ cells and other technical difficulties. The researchers hope that the success in mouse studies may spark the re-evaluation of human ROSI for its suitability to become an option for overcoming male infertility in the future.
- “Genetics discovery sheds new light on function of Y chromosome gene,”; January 5, 2016
- “Infertile mice generate offspring in assisted reproduction study,”; November 22, 2013
Read the John A. Burns School of Medicine news release for more about the discovery.