Notícias | Estudo da University of Hawaii constata: a perda de um gene essencial do cromossomo Y pode causar infertilidade em camundongos machos, afetando a expressão de centenas de genes
News | University of Hawaiʻi study finds: Deletion of key Y chromosome gene causes infertility in male mice and affects expression of hundreds of genes
In a new study, researchers at the John A. Burns School of Medicine (JABSOM) at the University of Hawaiʻi at Mānoa discovered that deletion of a key gene on the Y chromosome not only causes complete infertility in male mice, but also leads to abnormal expression of hundreds of important genes.
The study was led by Dr. Monika Ward, professor in the Department of Anatomy, Biochemistry and Physiology and the Yanagimachi Institute for Biogenesis Research (YIBR). The research team focused on the zinc finger Y-encoded gene Zfy, which is encoded by the Y chromosome. This gene exists in both humans and mice and is considered an important regulator of male reproduction. In mice, Zfy has two copies: Zfy1 and Zfy2.
Using CRISPR-Cas9 technology, the researchers successively generated transgenic mouse models with deletion of Zfy1 alone, Zfy2 alone, and both simultaneously (referred to as Zfy DKO, or Zfy double knockout). The results showed that Zfy DKO male mice were completely infertile, with severely abnormal sperm, and in the most extreme cases were unable to produce any sperm at all. This research was first published in 2022 in the journal Biology of Reproduction.
To further investigate the molecular mechanisms of Zfy deletion, the team used assisted reproductive technologies pioneered by YIBR founder Ryuzo Yanagimachi, including intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI), to successfully produce more Zfy DKO infertile male mice. The recent findings were published on 2025/8/27 in the international journal Cell Death and Differentiation.
The study indicated that in the absence of the Zfy gene, the expression of hundreds of genes in mice was dysregulated, with some genes overactivated and others suppressed. These genes include key genes regulating sperm formation, DNA packaging and conformation, and apoptosis. The team further found that sperm precursor cells in the testes underwent premature apoptosis, and even when sperm were occasionally produced, their DNA structure could not condense effectively and was highly susceptible to damage.
"This study has greatly advanced our understanding of Zfy gene function. We have identified the signaling pathways and related genes affected by it, and will further explore how Zfy regulates these key processes in the future," said Dr. Ward.
Dr. Ward also specifically noted that this research highlights the central role of University of Hawaiʻi undergraduate and graduate students in scientific research. The first author of the paper, Hayden Holmlund, who carried out most of the experimental work, is a recent PhD graduate of the Developmental and Reproductive Biology (DRB) graduate program and has now begun postdoctoral research in California. In addition, some experiments were completed by Benazir Yarbabaeva, an undergraduate INBRE program student, who has now joined the DRB program as a new master's student to continue exploring the mechanisms of Zfy DKO sperm.
"This study also reflects YIBR's core mission of promoting international collaboration in the field of reproductive and developmental biology," Dr. Ward added, noting that the research also received assistance from researchers in France and the United Kingdom.
This study represents a key step forward in understanding the mechanisms regulating male fertility and provides a foundation for future research on the regulatory role of Zfy in spermatogenesis. The knowledge gained through basic research using mouse models is not only important for the mechanistic management of male infertility, but also opens new directions for translational research into potential therapeutic strategies.
Notícias | Estudo da University of Hawaii constata: a perda de um gene essencial do cromossomo Y pode causar infertilidade em camundongos machos, afetando a expressão de centenas de genes
News | University of Hawaiʻi study finds: Deletion of key Y chromosome gene causes infertility in male mice and affects expression of hundreds of genes
In a new study, researchers at the John A. Burns School of Medicine (JABSOM) at the University of Hawaiʻi at Mānoa discovered that deletion of a key gene on the Y chromosome not only causes complete infertility in male mice, but also leads to abnormal expression of hundreds of important genes.
The study was led by Dr. Monika Ward, professor in the Department of Anatomy, Biochemistry and Physiology and the Yanagimachi Institute for Biogenesis Research (YIBR). The research team focused on the zinc finger Y-encoded gene Zfy, which is encoded by the Y chromosome. This gene exists in both humans and mice and is considered an important regulator of male reproduction. In mice, Zfy has two copies: Zfy1 and Zfy2.
Using CRISPR-Cas9 technology, the researchers successively generated transgenic mouse models with deletion of Zfy1 alone, Zfy2 alone, and both simultaneously (referred to as Zfy DKO, or Zfy double knockout). The results showed that Zfy DKO male mice were completely infertile, with severely abnormal sperm, and in the most extreme cases were unable to produce any sperm at all. This research was first published in 2022 in the journal Biology of Reproduction.
To further investigate the molecular mechanisms of Zfy deletion, the team used assisted reproductive technologies pioneered by YIBR founder Ryuzo Yanagimachi, including intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI), to successfully produce more Zfy DKO infertile male mice. The recent findings were published on 2025/8/27 in the international journal Cell Death and Differentiation.
The study indicated that in the absence of the Zfy gene, the expression of hundreds of genes in mice was dysregulated, with some genes overactivated and others suppressed. These genes include key genes regulating sperm formation, DNA packaging and conformation, and apoptosis. The team further found that sperm precursor cells in the testes underwent premature apoptosis, and even when sperm were occasionally produced, their DNA structure could not condense effectively and was highly susceptible to damage.
"This study has greatly advanced our understanding of Zfy gene function. We have identified the signaling pathways and related genes affected by it, and will further explore how Zfy regulates these key processes in the future," said Dr. Ward.
Dr. Ward also specifically noted that this research highlights the central role of University of Hawaiʻi undergraduate and graduate students in scientific research. The first author of the paper, Hayden Holmlund, who carried out most of the experimental work, is a recent PhD graduate of the Developmental and Reproductive Biology (DRB) graduate program and has now begun postdoctoral research in California. In addition, some experiments were completed by Benazir Yarbabaeva, an undergraduate INBRE program student, who has now joined the DRB program as a new master's student to continue exploring the mechanisms of Zfy DKO sperm.
"This study also reflects YIBR's core mission of promoting international collaboration in the field of reproductive and developmental biology," Dr. Ward added, noting that the research also received assistance from researchers in France and the United Kingdom.
This study represents a key step forward in understanding the mechanisms regulating male fertility and provides a foundation for future research on the regulatory role of Zfy in spermatogenesis. The knowledge gained through basic research using mouse models is not only important for the mechanistic management of male infertility, but also opens new directions for translational research into potential therapeutic strategies.
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