Gene Linked To Infertility In Mice; Findings May Apply To Humans

The research has not yet been conducted using human tissue, but Haifan Lin, an associate professor of cell biology at Duke and senior author of the study, suspects that the human counterpart of miwi, called hiwi, is probably also associated with infertility in men. The study could eventually lead to genetic testing for the human form of the miwi gene, Lin said.

Piwi and miwi stem from the piwi family of genes known to be associated with the division of reproductive stem cells, which are the immature cells that can proliferate and mature to become adult sperm cells.

"This study presents the first definitive evidence that the piwi gene family has an essential function in the mammalian male reproductive system," said Lin, who is senior author of the paper in the June 7, 2002, issue of Developmental Cell.

In a related paper that appears in the June 6, 2002 issue of Oncogene, Lin describes the connection between the human homologue of piwi, called hiwi, and testicular cancer. (Please visit http://www.dukemednews.org for a news release featuring the Oncogene paper.)

There are a number of genes linked to male infertility, but only two, which includes miwi and crem, have been directly linked to sperm production as master regulators, Lin said.

When the miwi gene is defective or missing, it can lead to complete sterility in mice, he said.

"We show that this gene, miwi, instructs the making of a protein that binds to messenger RNAs to control their life span," Lin said. Messenger RNAs, which constitute the genetic instructions for proteins, are copied from DNA to be used to direct the cell's protein-making machinery.

"In turn, these messenger RNAs control the process of sperm production. In short, the protein MIWI, which is encoded by this gene is a master protein responsible for turning genes on and off during the process of sperm formation," he said.

The testes of mice with a defective miwi gene were, on average, 29 percent smaller by weight and did