The loss of basal y chromosome gene causes infertility in male mice

In a new study conducted at the University of Hawai’i in Mānoa, researchers at the John A. Burns (Jabsom) medical school showed that the loss of a basic fertility gene genes infertility and changes the expression of hundreds of significant genes.

The study was led by Professor Dr. Monika Ward from the Department of Anatomy, Biochemistry & Physiology and the Yanagimachi Yibr Research Institute. The group has investigated a gene encoded by zinc y that is called Zfy. This gene, encoded on a Y chromosome in mice and humans, is considered a male fertility factor. In mice, Zfy They are present as two copies, zfy1 and zfy2.

Researchers first used CRISPR-CAS9 to produce knockout mice specifically Zfy1; Zfy2both Zfy1 and Zfy2 genes, the latter called Zfy DKO (Zfy double knockout). They noticed it Zfy The dko males were completely sterile and had severe abnormal sperm. In the most serious cases, Zfy DKO male could not produce any sperm. These findings were published in 2022, in Breeding biology.

The group then applied assisted reproduction technologies (ART) to produce more sterile Zfy DKO males so that the surveys of these mice can continue. They used intracellular sperm injection (ICSI) and a round injection of sperm (ROSI) – techniques pioneered at the University of Hawai’i by Yibr founder, Ryuzo Yanagimachi. In the new study, published on August 27 Cell death and differentiationThe group shows the molecular consequences of Zfy loss.

Researchers have shown that without Zfy Hundreds of genes become liberated, expressed either very intense or very weak. Among these genes are those responsible for the production of sperm, for the packaging and organization of DNA and for cell death. The group linked the release of these genes to testicles and sperm changes. They found that the precursors of sperm in the testicles died prematurely and the sperm, if produced, had DNA that was not properly concentrated and therefore vulnerable to damage.

This project really promotes our understanding of how this important Zfy General works. We have identified trails and other genes affected and now we can study exactly how Zfy It regulates them. ”

Dr. Monika Ward, Professor, Department of Anatomy, Biochemistry & Physiology and Yanagimachi Institute for Biogenesis Research (Yibr)

“This study is an example of a critical role played by undergraduate and postgraduate students at the University of Hawai’i. Benazir Yarbabaeva, who just started as a MS student in the DRB program to continue his exploration Zfy DKO sperm, “Dr. Ward continued.

“Finally, the study is an example of Yibr’s basic mission.” said Dr. Ward. Yibr promotes cooperation in reproductive and developmental biology beyond. “The new study was carried out with contributions by colleagues from France and England”

The study represents an important step forward in our understanding of how male fertility is regulated and opens the way for future explorations Zfy Regulatory role in sperm production. The fundamental knowledge received through basic research using mice as a model face a specific need for health – the management of male fertility/treatment of male infertility – and has translation effects.