Male infertility is a complex issue that affects many couples trying to conceive. Recent research conducted by scientists at the University of Hawaiʻi at Mānoa has shed light on a crucial link between a missing Y chromosome gene and male infertility. The study, published in Cell Death & Differentiation, revealed that deleting a single gene in mice led to infertility and disrupted hundreds of other genes essential for healthy sperm production.
The focus of the study was on the Zfy gene, found on the Y chromosome in both humans and mice. In mice, there are two versions of this gene: Zfy1 and Zfy2. Using CRISPR gene-editing technology, the researchers created mice missing one or both versions of the gene. Males without both versions, known as Zfy double knockouts, were found to be completely infertile, with severely abnormal or absent sperm.
Lead researcher Monika Ward emphasized the significance of the findings, stating, “This work really pushes forward our understanding of how this important Zfy gene works. We identified pathways and other genes that are affected, and we can now study how exactly Zfy regulates them.” To further investigate the molecular consequences of Zfy loss, the team utilized assisted reproduction techniques such as intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI).
The results of the study revealed that without the Zfy gene, hundreds of other genes became misregulated, impacting sperm production, DNA packaging, and cell survival. Sperm precursor cells in the testes died prematurely, and the sperm that did form carried fragile DNA that was not properly condensed.
The research also highlighted the contributions of students to the project. Hayden Holmlund, the study’s first author, completed his Ph.D. at UH and is now a postdoctoral fellow in California. Undergraduate student Benazir Yarbabaeva also played a role in the research and has since joined the graduate program to continue her studies.
The collaborative nature of the study, involving colleagues from France and England, underscores the importance of global partnerships in advancing scientific research. The findings offer valuable insights into the genetic mechanisms underlying male infertility and may pave the way for new diagnostic and treatment strategies in the future.
For more information on the study, the research paper titled “Large-scale transcriptomic analyses reveal downstream target genes of ZFY1 and ZFY2 transcription factors in male germ cells” can be accessed in Cell Death & Differentiation. The research is a significant step forward in understanding male infertility and its genetic underpinnings.
