News | Crick Institute identifies links between Y-chromosome genes and sperm development
Researchers at the Crick Institute have identified which Y-chromosome genes regulate sperm development and affect fertility in male mice. The study may improve understanding of why some men have low sperm counts that lead to infertility.
Men typically have one X and one Y chromosome, while women have two X chromosomes. Although the Y chromosome is known to be essential for male fertility, the specific genes and mechanisms involved remain poorly understood.
In a study published today in Science, the Crick team created 13 different mouse models, each lacking different Y-chromosome genes, to investigate their roles in fertility.
The researchers assessed the adult mice's reproductive capacity, including offspring numbers, sperm counts, sperm morphology, and motility. Several Y-chromosome genes proved essential for reproduction. Without them, mice could not reproduce because of low sperm counts, depleted spermatogonial stem-cell reserves, or abnormal sperm morphology and motility.
Surprisingly, loss of some individual genes did not affect fertility, but loss of several genes together caused sperm abnormalities. This was demonstrated in three genes corresponding to the human AZFa region. AZFa deletions are a common cause of the most severe forms of male infertility, but it has been difficult to determine which genes in this region are responsible.
The findings indicate that multiple Y-chromosome genes work together in male fertility and can compensate for one another when one gene is lost. Some cases of infertility may therefore result from the simultaneous loss of several genes.
Beyond sperm production, some Y-linked genes also function in organs such as the heart and brain and may be highly important. Some men also lose the Y chromosome from blood cells with age because of cell-division errors; this loss has been associated with conditions including Alzheimer's disease and cancer. The team is therefore studying changes in other organs of mice lacking Y-linked genes.
First author Jeremie Subrini, a postdoctoral research associate at the Crick Institute, said: "Our research shows that more Y-chromosome genes than expected are essential for fertility in mice. Some genes are indispensable, while others have cumulative effects. The Y chromosome has long been misunderstood as unnecessary in adults, and some have even suggested it will disappear. We can now say with confidence that this hypothesis is incorrect."
Senior author Professor James Turner, head of the Sex Chromosome Biology Laboratory at the Crick Institute, added: "Infertility is a serious issue, with around one in six couples worldwide having difficulty conceiving. In many cases, genetic factors—particularly Y-chromosome problems—cause infertility. The details have remained elusive, partly because sequencing and studying the Y chromosome has been technically challenging."
"Now that we have identified the roles of Y-chromosome genes, the next step is to sequence the Y chromosomes of more individuals to uncover potential causes of male infertility. With further research, we may be able to help infertile couples conceive through IVF and perhaps even compensate for missing Y-linked genes."
News | Crick Institute Links Y-Chromosome Genes to Sperm Development
News | Crick Institute identifies links between Y-chromosome genes and sperm development
Researchers at the Crick Institute have identified which Y-chromosome genes regulate sperm development and affect fertility in male mice. The study may improve understanding of why some men have low sperm counts that lead to infertility.
Men typically have one X and one Y chromosome, while women have two X chromosomes. Although the Y chromosome is known to be essential for male fertility, the specific genes and mechanisms involved remain poorly understood.
In a study published today in Science, the Crick team created 13 different mouse models, each lacking different Y-chromosome genes, to investigate their roles in fertility.
The researchers assessed the adult mice's reproductive capacity, including offspring numbers, sperm counts, sperm morphology, and motility. Several Y-chromosome genes proved essential for reproduction. Without them, mice could not reproduce because of low sperm counts, depleted spermatogonial stem-cell reserves, or abnormal sperm morphology and motility.
Surprisingly, loss of some individual genes did not affect fertility, but loss of several genes together caused sperm abnormalities. This was demonstrated in three genes corresponding to the human AZFa region. AZFa deletions are a common cause of the most severe forms of male infertility, but it has been difficult to determine which genes in this region are responsible.
The findings indicate that multiple Y-chromosome genes work together in male fertility and can compensate for one another when one gene is lost. Some cases of infertility may therefore result from the simultaneous loss of several genes.
Beyond sperm production, some Y-linked genes also function in organs such as the heart and brain and may be highly important. Some men also lose the Y chromosome from blood cells with age because of cell-division errors; this loss has been associated with conditions including Alzheimer's disease and cancer. The team is therefore studying changes in other organs of mice lacking Y-linked genes.
First author Jeremie Subrini, a postdoctoral research associate at the Crick Institute, said: "Our research shows that more Y-chromosome genes than expected are essential for fertility in mice. Some genes are indispensable, while others have cumulative effects. The Y chromosome has long been misunderstood as unnecessary in adults, and some have even suggested it will disappear. We can now say with confidence that this hypothesis is incorrect."
Senior author Professor James Turner, head of the Sex Chromosome Biology Laboratory at the Crick Institute, added: "Infertility is a serious issue, with around one in six couples worldwide having difficulty conceiving. In many cases, genetic factors—particularly Y-chromosome problems—cause infertility. The details have remained elusive, partly because sequencing and studying the Y chromosome has been technically challenging."
"Now that we have identified the roles of Y-chromosome genes, the next step is to sequence the Y chromosomes of more individuals to uncover potential causes of male infertility. With further research, we may be able to help infertile couples conceive through IVF and perhaps even compensate for missing Y-linked genes."
Source:
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