Males usually have one X and one Y chromosome, while females have two X chromosomes. The mammalian Y chromosome, though small, contains several gene families involved in spermatogenesis and fertility. However, the question of which Y genes regulate spermatogenesis is unresolved.
A research team at the Crick created thirteen mouse models, each missing different Y genes, to study their fertility. Their findings revealed which Y chromosome genes regulate sperm development and affect male fertility.
Researchers examined the reproductive ability of adult mice, including offspring numbers, sperm production, and sperm appearance and movement. They found several Y genes crucial for reproduction.
Removing these genes resulted in no or fewer sperm, no sperm stem cells, or abnormal sperm shape or movement. Some genes had no effect when removed individually but caused abnormal sperm when removed together.
Three genes in a chromosome region called AZFa are linked to severe male Infertility. The results show many Y genes impact fertility and can compensate for each other. Infertility may result from multiple genes being deleted.
Scientists identify genetic factors responsible for infertility among Indian men
Some Y genes are also active in organs like the heart and brain. As men age, losing Y chromosomes in blood is linked to conditions like Alzheimer’s or cancer. Researchers are studying other organs in mice with Y gene deletions.
Jeremie Subrini, Postdoctoral Research Assistant in the Sex Chromosome Biology Laboratory at the Crick, the first author, said: “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. It wasn’t considered essential in adults for a long time, and some even hypothesised that it would disappear altogether. We now know that this is clearly not the case!”
– Jeremie Subrini
James Turner, Principal Group Leader of the Sex Chromosome Biology Laboratory at the Crick and senior author, said: “Infertility is a big problem, with 1 in 6 couples struggling to conceive. Genetic factors, particularly those involving the Y chromosome, cause many cases. However, the details have been difficult to pinpoint, partly because sequencing and studying the Y chromosome has been technically challenging.”
“Now that we’ve shed light on the Y genes, it will be important to start sequencing the Y chromosome in more individuals to uncover unexplained causes of male infertility potentially. 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.”
Journal Reference:
- Jeremie Subrini, Wazeer Varsally Irina Balaguer Balsells et al. Systematic identification of Y-chromosome gene functions in mouse spermatogenesis. Science. DOI: 10.1126/science.ads6495
Source: Tech Explorist
