Genes on the Y chromosome that regulate the development of sperm and influence fertility in male mice have been identified.
In order to understand the role Y-chromosome genes play in fertility, researchers in the sex chromosome biology laboratory at the Francis Crick Institute, London, generated a number of mouse models with different genes on the Y chromosome removed. By recording the ability of these mice to have offspring, the number of offspring produced, and the quality and number of sperm produced, they were able to identify which genes were critical for reproduction.
'Our research has shown that more Y genes are required for mouse fertility than first thought. We saw that some genes are crucial, but others have a cumulative effect. Historically, the Y chromosome has been misunderstood. For a long time, it wasn't thought to be essential in adults, and some even hypothesised that it was going to disappear altogether. We now know that this is clearly not the case!' said Dr Jeremie Subrini, first author of the paper, published in Science, and postdoctoral research assistant at the Francis Crick Institute.
They discovered that some genes work together to produce normal sperm, compensating for each other if one was knocked out. One example of this was the AZFa region in humans, where we know deletions can result in male infertility. This research follows the completion of a reference genome for the human Y chromosome, from sequencing efforts reported in 2023 (see BioNews 1204).
'Infertility is a big problem, with one in six couples struggling to conceive. In a significant proportion of cases, genetic factors, particularly those involving the Y chromosome, are the cause. However, the details have been difficult to pinpoint, partly because sequencing and studying the Y chromosome has been technically challenging,' Dr James Turner, senior author and principal group leader of the group at the Francis Crick Institute, commented.
He continued: 'Now that we've shed light on the Y genes, it will be important to start sequencing the Y chromosome in more individuals, to potentially uncover unexplained causes of male infertility. With more research, we may be able to one day replace missing genes in the cells that make sperm to help couples have children through IVF'.
The researchers hope that these findings will help to understand male fertility issues, such as why some men do not produce enough sperm and are infertile.
Further research in the laboratory is focusing on identifying how loss or alterations in Y-chromosome genes can impact other organs, as they have previously been linked to conditions such as cancer and Alzheimer's disease.
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