Researchers at the University of Hawai'i at Mānoa have uncovered a direct link between the absence of a Y chromosome gene, Zfy, and male infertility through their studies on mice, which could have significant implications for human reproductive health.

Using CRISPR gene-editing, the team created Zfy double knockout mice, revealing that the loss of both Zfy1 and Zfy2 causes early death of sperm precursor cells and results in fragile, improperly condensed DNA in sperm.

The knockout mice exhibited severe sperm development issues, including defective tail structures, reduced testis size, and sperm with abnormal, circular movements instead of normal progressive swimming.

The deletion of Zfy genes disrupted hundreds of genes involved in sperm production, DNA packaging, and cell survival, highlighting the gene's broad regulatory role in male fertility.

Further, the absence of Zfy impacted the expression of apoptosis-related genes and affected sperm motility, emphasizing its importance in sperm development and function.

The study's key contributors include first author Hayden Holmlund and undergraduate Benazir Yarbabaeva, with collaborative efforts extending to researchers in France and England.

In human cells, ZFY overexpression influences apoptosis genes but does not significantly affect sex-linked genes, suggesting a broader biological role beyond just sperm production.

While the findings have potential implications for understanding and treating male infertility, the gene's functions appear more extensive in humans compared to mice, which have two variants of the gene.

In humans, ZFY is expressed throughout the body and differs from mice, which possess two variants of the gene; humans have only ZFY on the Y chromosome and a related gene, ZFX, on the X chromosome.

These insights into the genetic regulation of male fertility could inform future treatments for infertility associated with Y chromosome anomalies.

The research employed advanced assisted reproductive techniques like ICSI and ROSI to study the molecular effects of Zfy loss and assess sperm quality.

The disruption of hundreds of genes related to apoptosis and DNA packaging underscores the Zfy gene's extensive regulatory influence in sperm development.