A team of researchers from the Crick Institute has identified key genes on the Y chromosome that play a pivotal role in sperm development and male fertility. This breakthrough could provide answers to why some men struggle with infertility due to low sperm production.
While males typically have one X and one Y chromosome, and females have two X chromosomes, the role of the Y chromosome in male fertility has long been understood, but the specific genes responsible for regulating this process were unclear.
In a study published today in Science, the Crick team tackled this challenge by creating thirteen distinct mouse models, each with a different Y gene removed. The researchers then examined how these genetic modifications affected the mice’s reproductive abilities, including sperm production, sperm quality, and their ability to reproduce.
The results revealed that several Y chromosome genes are essential for male fertility. When these genes were deleted, the mice failed to reproduce due to factors such as insufficient sperm production, defective sperm motility, or abnormal sperm shape. Some genes appeared harmless when deleted individually but caused issues when removed in combination, leading to abnormal sperm development.
Among the most significant findings were those related to a region of the Y chromosome known as AZFa, which is linked to severe male infertility in humans. Deletions in this region are commonly observed in cases of male infertility, but pinpointing the exact genes responsible has been difficult. This research suggests that a cluster of Y genes work together to ensure proper sperm development, and the loss of multiple genes may result in infertility.
In addition to their role in reproduction, certain Y chromosome genes were also active in other organs, such as the heart and brain. The study also raised awareness about the loss of Y chromosomes in blood cells due to errors in cell division as men age, which is associated with diseases like Alzheimer’s and cancer. The team plans to further investigate the impact of Y gene deletions on other organs in these mice models.
Jeremie Subrini, a postdoctoral research assistant at the Crick Institute and the study’s first author, emphasized the importance of these findings, saying, “Our research has shown that the Y chromosome plays a more complex role in fertility than previously thought. It was once believed that the Y chromosome might eventually disappear, but this research clearly shows that it is crucial for male health.”
James Turner, the principal investigator of the study, added, “Infertility affects about 1 in 6 couples, and genetic factors, especially those involving the Y chromosome, are often to blame. Understanding the specific role of Y genes will help uncover the genetic causes of male infertility, allowing for more targeted treatments, including potential gene replacement therapies in the future.”
As this research continues, the next step is to sequence the Y chromosome in more individuals, offering hope for developing new approaches to treat male infertility through assisted reproductive technologies such as IVF.
Related topics:
Seminal Fluid, Not Sperm, Key to Male Reproductive Decline with Age, Study Finds
Birla Fertility & IVF Lajpat Nagar Centre Celebrates Three Years of Exceptional Care
