Researchers at the Francis Crick Institute have identified specific genes on the Y chromosome that regulate sperm development and influence male fertility in mice. This breakthrough may shed light on why some men produce insufficient sperm and face infertility.
Humans possess 23 pairs of chromosomes, including sex chromosomes (XX in females and XY in males). While other chromosomes contain thousands of genes, the Y chromosome has only a few dozen. The study, published in the journal 'Science', utilized thirteen mouse models with different Y chromosome genes deleted to assess their impact on fertility.
The team evaluated the reproductive capacity of adult mice by observing offspring count, sperm production, and sperm morphology and motility. Several essential genes for reproduction were identified: their deletion led to a lack or reduction of sperm, failures in spermatogonial stem cell production, or abnormalities in sperm shape and movement.
Interestingly, some genes did not affect fertility individually, but their combined deletion resulted in abnormal sperm. This was observed in three genes modeling the AZFa region of the human Y chromosome, whose deletion is a common cause of severe male infertility.
The findings indicate that many Y chromosome genes have complementary roles in fertility, compensating for each other when one is absent. This explains why certain infertility forms may arise from the simultaneous deletion of multiple genes.
Additionally, some Y chromosome genes are also active in organs such as the heart and brain, which may have implications in diseases like Alzheimer’s or cancer, particularly in older men who lose Y chromosomes in blood due to errors in cell division.
Jeremie Subrini, the lead author, notes that the research demonstrates that more Y chromosome genes are necessary for fertility than previously thought. While some are critical, others have cumulative effects. Historically, he states, 'the Y chromosome has been misunderstood; we now know it is essential.'
Senior author James Turner adds that 'infertility affects 1 in 6 couples, and in many cases, genetic factors, particularly those related to the Y chromosome, are the cause. This work paves the way for sequencing the Y chromosome in more individuals to identify unknown causes of male infertility. With further research, we could replace absent genes in sperm-producing cells to assist couples through IVF.'