Scientists created male mice able to reproduce without Y chromosomes

February 1, 2016  10:47

Mice whose Y chromosomes have been replaced with just two genes are still able to father offspring, demonstrating the unexpected complexity of reproductive genetics.

High school genetics has a simple story about sex chromosomes: Women have two X chromosomes, while men have an X and a Y. The presence of a Y chromosome is what defines biological maleness. Sometimes more unusual situations, such as XXY or XYY, get a mention, but reproduction without a Y is something new.

The Y chromosome is much smaller than the X, carrying far fewer genes. In 2014, Professor Monika Ward of the University of Hawaii revealed that only two of these Y chromosome genes, known as Sry and Eif2s3y, are enough to enable male mice to reproduce, even if the rest of the chromosome is removed.

Sry, for "sex-determining region Y," targets the Sox9 gene, which sits on the 17th chromosome in humans and the 11th in mice, rather than on the sex chromosomes. Ward cut out the “middle gene” by removing the entire Y chromosome and promoting the overexpression of Sox9, which promotes testes development. Previous work showed that overexpressing Sox9 in genetically female (XX) mice caused them to develop male characteristics. Ward also encouraged greater expression of the gene Eif2s3x on the X chromosome with a similar structure to Eif2s3y, a gene crucial to sperm formation, or spermatogenesis.

Some of the engineered mice produced sperm, and Ward and her colleagues report in Science that when they attempted to artificially inseminate female mice with their product, at least 10 of the Y-less mice were fertile.

Not all of these mice, dubbed X0 for having a single X chromosome without a match, turned out well, with 35 out of 48 having testicular defects and a lack of sperm. Using sperm from the other 13 mice, 10 led to pregnancies and nine to live births. All of these, Ward told IFLScience, were healthy and lived normal-length lives for rats.

The authors note that the more highly expressed the Eif2s3x genes were, the further the mice got through the sperm production process.

“We are currently not working towards any specific application,” Ward told IFLScience. “We want to advance the understanding of Y chromosome gene function, and understanding of X-Y gene pairs.”

She added: “Our findings could be, however, applied to the development of bi-maternal reproduction, where one female would generate sperm and the other oocytes, or one female would generate both. Demonstrating that this could be done is interesting from a basic science point of view and would support the plasticity of the genome.”

“There might be a practical value in this too,” Ward continued. “Such an alternative form of reproduction could, for example, be applied in species preservation. If we end up with just one female of a given species, being able to develop both male and female gametes from one individual would help to prevent its extinction. Bi-maternal reproduction might also be useful in agriculture, if it is more desirable to combine genetic material from two females rather than from a female and a male.”

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