A five-year study at the University of Hawaiʻi’s medical school will investigate how a key gene, called Zfy, impacts sperm production and fertility. Funded by a $2.4 million grant from the National Institutes of Health, the research aims to uncover new insights into male reproduction and tackle infertility challenges.
“The Zfy gene is an essential male fertility factor, but how it imposes its important role has not been established,” said lead researcher Monika Ward, professor of anatomy, biochemistry, and physiology at UH Mānoa’s John A. Burns School of Medicine (JABSOM). “If we want to overcome the overarching issue of infertility, we must have a deep understanding of the processes that underlie fertility.”
Ward, who has dedicated nearly 30 years to studying male infertility, believes this research could open new pathways for addressing fertility issues and improving overall health outcomes.
Unlocking the mysteries of Zfy
The Zfy gene was once thought to determine an animal’s sex, but interest faded when that theory was disproved. Decades later, new evidence has linked Zfy to fertility, sparking renewed interest in its function. Ward’s team used mouse models to study how the gene’s absence affects sperm production and fertility.
The study found that mice missing both Zfy1 and Zfy2 genes are completely infertile, producing malformed sperm with poor motility. However, when only one gene is absent, the effects are less severe but still significant.
Researchers will also examine how Zfy interacts with other genes in the testes and whether the ZFY protein directly binds to DNA to regulate fertility-related processes.
Advanced techniques in fertility research
The team has developed specialized mouse models, including those that lack Zfy genes or feature tagged ZFY proteins. They are also using advanced assisted reproduction techniques to propagate infertile mice, enabling the generation of critical tissue samples for molecular analysis.
“The findings will impact our understanding of how mouse Zfy regulates sperm production and will provide vital insights into the role of how the human ZFY is connected to mechanisms underlying human male infertility,” Ward said.
