Does the y-chromosome a male make? When it comes to mice, a new study shows the answer is: nope.
Since it was discovered more than 100 years ago, the y chromosome—a chain of genes connected to male development in mammals—has become a symbol of masculinity. But in a paper published today in the journal Science, researchers showed that it’s possible for male mice with no y-chromosome to successfully reproduce. These findings advance a long line of questioning around what exactly the function of this chromosome is.
“The y-chromosome is unique in that it wasn’t possible until very, very recently to target the function of these genes,” said Monika Ward, a genetics researcher at the University of Hawaii and co-author of the study. “We’re really interested in investigating the function of this chromosome’s genes.”
Two years ago, Ward and her fellow researchers showed that only two genes from the Y-chromosome were needed for a male mouse to produce offspring through assisted reproduction: SRY and Eif2s3y. (Gene names are never very catchy, but bear with me.) SRY signals the fetus to develop as male and Eif2s3y is responsible for initiating sperm production. For this experiment, the researchers wanted to take it a step further and see if it was possible for male mice to produce offspring without any y-chromosome genes at all.
To do this, Ward and her team replaced these two y-chromosome genes with ones from the x-chromosome. SRY was replaced with a gene that is usually activated by SRY, and is “next in line,” Ward said. Instead of leaving SRY to activate this gene, the researchers activated it manually. Eif2s3y was replaced by overexpressing the x-chromosome gene that works in tandem to tell the mouse to start producing sperm.
The results weren’t perfect, so to speak. These y-chromosome-less males had smaller than normal testes and couldn’t produce mature sperm, only round spermatids—early-stage sperm cells that haven’t yet developed tails. No tails means no swimming, so natural breeding wasn’t possible. But the researchers were able to successfully produce offspring using in vitro fertilization. The male offspring of the no-y-chromosome mice were completely infertile, but the female offspring were able to reproduce normally and even produce completely fertile male sons.
The bottom line: the grandsons of the y-less mice were able to reproduce normally. All of the mice were otherwise normal and healthy, too, Ward said.
“We still have several of them living in our animal colony,” Ward told me. “They’re more than two years old right now. The average lifespan of mice is two years, so they’re doing well.”
So what does it all mean? Is the y-chromosome as a symbol of masculinity just an illusion? This is a question researchers have been grappling with for years. The y-chromosome has been degrading throughout evolution and some mammals have no y-chromosomes at all. In light of this, researchers like Ward are trying to pinpoint exactly what the function of the y-chromosome genes are to help us understand this puzzle. This latest finding, for example, helped further our understanding of how each gene functions, what we can do without it, and what we can’t.
“We had to do reproduction using in vitro. In a normal situation, the y-chromosome is still badly needed for male fertility,” Ward told me, adding she's not on a mission to disrupt our understanding of maleness. “All of the other genes on the y-chromosome are responsible for something—male fitness, sperm production, sperm count. We’re not trying to eradicate the y-chromosome or males. I’m actually looking forward to many years of studying it, so I want y-chromosomes.”