New mouse models to study a key male fertility gene, providing insights that could help scientists understand and eventually treat male infertility, were developed by researchers at the University of Hawaiʻi at Mānoa . The study, published in BMC Genomics , builds on years of research into how this gene functions in male reproductive cells.
The work, led by Professor Monika Ward of the John A. Burns School of Medicine and the Yanagimachi Institute for Biogenesis Research , focuses on the Y chromosome gene ZFY, which is critical for male fertility. In earlier studies , the team demonstrated that male mice lacking both copies of Zfy were completely infertile and showed widespread disruption of genes involved in sperm development and cell survival.
New tools to track ZFY proteins
In the newly accepted study, the team used CRISPR–Cas9 genome editing to add molecular "tags" to the two mouse versions of Zfy, known as Zfy1 and Zfy2. These tags make it possible to detect, isolate and study the proteins in unprecedented detail.
Related UH News story: Missing Y gene linked to male infertility
Using the tagged mouse models, the researchers were able for the first time to identify which male germ cells produce Zfy1 and Zfy2 proteins and at what levels.
"We now know which male germ cells express which Zfy proteins, and how strongly," said Ward.
Because ZFY is thought to act as a transcription factor-switching other genes on and off-the new models could help identify which genes it regulates, offering critical insights that may one day guide diagnosis and treatment of male infertility.
"We have been after the Zfy genes for a long time! We knew how important Zfys are for male fertility for quite a while but were unable to learn how exactly they work," Ward said. "The new mice represent a much-needed tool to continue the investigations to determine how Zfy controls spermatogenesis."
