Researchers have identified specific genes on the Y chromosome that influence sperm development and male fertility in mice. This discovery could provide insights into why some men experience low sperm production and infertility.
Researchers at the Crick Institute have pinpointed genes on the Y chromosome that play a role in sperm development and male fertility in mice. This findings may help us understand the reasons behind low sperm counts and infertility in some men.
Males generally have one Y chromosome and one X chromosome, while females typically have two X chromosomes. Although the necessity of the Y chromosome for male fertility is established, the specific genes that are crucial and their mechanisms remain somewhat ambiguous.
In a study published today in Science, the Crick research team addressed this uncertainty by creating thirteen distinct mouse models, each lacking different Y genes, and examined their fertility.
The researchers assessed the reproductive capabilities of the adult mice by analyzing the number of offspring produced, the volume of sperm generated, and the physical characteristics and movement of the sperm.
They discovered that several Y genes are vital for successful reproduction. Mice missing these genes were unable to have offspring due to insufficient or absent sperm production, failure to generate a supply of sperm stem cells, or abnormal sperm shapes and motility.
Interestingly, certain genes did not lead to issues when eliminated on their own but resulted in abnormal sperm when several were removed simultaneously.
This was particularly shown in a group of three genes that correlate with a region on the chromosome known as AZFa in humans. Deletions in the AZFa region are a frequent cause of severe male infertility, yet pinpointing the responsible genes has been challenging.
The findings indicate that numerous Y genes contribute to fertility and can adjust to compensate if one gene is absent. This suggests that some infertility cases may stem from the loss of multiple genes concurrently.
In addition to their role in sperm production, some Y genes also function in other organs like the heart and brain, where they may be crucial. Furthermore, as men age, they might lose their Y chromosomes in blood due to mistakes during cell division. This loss has been linked with conditions such as Alzheimer’s disease and cancer, prompting further investigation into the effects of Y gene deletions in other organs of the mice.
Jeremie Subrini, a Postdoctoral Research Assistant in the Sex Chromosome Biology Laboratory at the Crick, and the lead author, commented: “Our study has revealed that more Y genes are necessary for fertility in mice than previously understood. We observed that while some genes are essential, others contribute cumulatively. The significance of the Y chromosome has often been underestimated. For a long time, it was thought to be non-essential in adults and even predicted to vanish entirely. Clearly, that isn’t the case!”
James Turner, the Principal Group Leader of the Sex Chromosome Biology Laboratory at the Crick, and senior author, stated: “Infertility poses a significant challenge, affecting 1 in 6 couples trying to conceive. Genetic issues, especially involving the Y chromosome, are a common cause in many cases. However, detailed understanding has been elusive due to the technical challenges of sequencing and examining the Y chromosome.”
“With our new insights into Y genes, it will now be essential to sequence the Y chromosome in a broader population to potentially discover unexplained causes of male infertility. With further research, we could one day replace missing genes in sperm-producing cells, assisting couples in having children through IVF.”
