Two Y genes can replace the entire Y chromosome for assisted reproduction in mice

Nov 21, 2013
This is a close up of the micromanipulation Petri dish, in which oocytes are injected with round spermatids. Also visible are gamete holding (left) and injecting (right) glass pipettes. The procedure is done under 200x magnification on the stage of an inverted microscope. Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawai'i. Credit: David Beales

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.

"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'i. At the same time, however, she also emphasized the importance of the Y chromosome for normal, unassisted fertilization and other aspects of .

In a new manuscript scheduled for online publication in the journal Science on November 21, 2013, Ward and her UH colleagues describe 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.

For this study, 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 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.

This is a mature daughter of the male with two Y genes obtained by ROSI. The female is healthy and fertile, and here it is shown with her own litter. Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawai'i. Credit: Monika A. Ward

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. At present, ROSI is still considered experimental due to concerns regarding the safety of injecting immature germ cells and other technical difficulties. The researchers hope that the success of ROSI in mouse studies may serve to support this approach as a viable option for overcoming infertility in men in the future.

As for the human Y chromosome, the researchers agree that it's not on its way to oblivion. Its genetic information is important for developing mature sperm and for its function in normal fertilization. The same is true for mice.

"Most of the mouse Y chromosome genes are necessary for normal fertilization," Ward said. "However, when it comes to , our mouse study proves that the Y chromosome contribution can be brought to a bare minimum. It may be possible to eliminate the Y chromosome altogether if appropriate replacements are made for those two ."

Explore further: The origin of the language of life

More information: "Two Y Genes Can Replace the Entire Y Chromosome for Assisted Reproduction in the Mouse," by Y. Yamauchi et al. Science, 2013.

Related Stories

Unravelling the secrets of maleness

Sep 05, 2013

New research has identified the key to becoming male is an enzyme that "unravels" DNA to trigger male development of the embryo, a discovery that may give greater insight into intersex disorders.

Research finds X doesn't always mark the spot

Sep 25, 2013

Research from the University of Bath has found a greater number of 'escaping genes' on the X chromosome than have been previously detected, with implications for the understanding of mental impairment in humans.

Homing in on developmental epigenetics

Aug 23, 2013

Germ cells have unique molecular features that enable them to perform the important task of transmitting genetic information to the next generation. During development from their embryonic primordial state, ...

Recommended for you

The origin of the language of life

Dec 19, 2014

The genetic code is the universal language of life. It describes how information is encoded in the genetic material and is the same for all organisms from simple bacteria to animals to humans. However, the ...

Quest to unravel mysteries of our gene network

Dec 18, 2014

There are roughly 27,000 genes in the human body, all but a relative few of them connected through an intricate and complex network that plays a dominant role in shaping our physiological structure and functions.

EU court clears stem cell patenting

Dec 18, 2014

A human egg used to produce stem cells but unable to develop into a viable embryo can be patented, the European Court of Justice ruled on Thursday.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.