Scientists have created male mice without a Y chromosome - a symbol of maleness - that are still able to sire offspring with assisted reproduction.
Scientists have created male mice without a Y chromosome – a symbol of maleness – that are still able to sire offspring with assisted reproduction.
The Y chromosome is present only in males and encodes genes important for male reproduction. But a new study has shown that live mouse progeny can be generated with assisted fertilisation using germ cells from males which do not have any Y chromosome genes.
The findings support the hypothesis that Y chromosome genes can be replaced by that encoded on other chromosomes.
Previous research showed 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 fertilisation.
In the current study, researchers led by Monika A Ward, professor at the University of Hawaii, took a step further and produced males completely devoid of the entire Y chromosome.
They first replaced the Y chromosome gene Sry with its homologue and direct target encoded on chromosome 11, Sox9.
In normal situation, Sry activates Sox9, and this initiates a cascade of molecular events that ultimately allow an XY foetus to develop into a male. The researchers used transgenic technology to activate Sox9 in the absence of Sry.
They replaced the second essential Y chromosome gene, Eif2s3y, with its X chromosome encoded homologue, Eif2s3x.
Eif2s3y and Eif2s3x belong to the same gene family and are very similar in sequence. The researchers speculated that these two genes may play similar roles, and it is a global dosage of both that matters.
They transgenically over expressed Eif2s3x, increasing dose of the X gene beyond that provided normally by X and Y. Under these conditions, Eif2s3x took over the function of Eif2s3y in initiating spermatogenesis.
They then replaced Sry and Eif2s3y simultaneously, and created XOSox9, Eif2s3x males that had no Y chromosome DNA. Mice lacking all Y chromosome genes developed testes populated with male germ cells.
Round spermatids were harvested and a technique called round spermatid injection (ROSI) was used to successfully fertilise oocytes.
When the developed embryos where transferred to female mouse surrogate mothers, live offspring were born.
The offspring derived from the “No Y” males were healthy and lived for normal life span. The daughters and grandsons of the “No Y” males were fertile and capable of reproducing on its own without further technological intervention.
Researchers produced three consecutive generations of “No Y” males showing that males lacking Y chromosome genes can be repeatedly propagated with technical assistance.
“Most of the mouse Y chromosome genes are necessary for development of mature sperm and normal fertilisation, 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,” she said.
The study was published in the journal Science.