The Gene of Male Infertility Finally Found

It's easy to blame it on the woman, but in 15 % of cases, the guilt can be attributed to the stud.

Now Cornell study could bring more hope for these couples, as a research team detected a gene mutation that induces male infertility in mice.

This is the first dominant mutation found to specifically trigger infertility in a mammal and the researchers can now investigate similar mutations in infertile men. "If you consider infertility a disease, you can't study it like you would other diseases, because the affected people can't reproduce," said senior author John Schimenti, director of Cornell's Center for Vertebrate Genomics. "Consequently, we know very little about the genetic causes of infertility in humans," said Schimenti, a Cornell professor of genetics.

The Dmc1gene encodes a protein involved in meiosis, the cell division that delivers sperm and egg cells.

These sex cells present just one set of chromosomes that combine during fertilization, resulting a fertilized egg with two chromosome sets, one from the male and one from the female.

The fertilized egg further develops into an embryo.

The mutant Dmc 1 produces an ineffective protein that cannot work in the meiosis, and whose blocking means no sperm synthesis. The mutant is dominant; females carrying it are fertile but pass the defective gene to future generations, and males who inherit it are sterile as they can not produce sperm.

Moreover, female carriers display higher levels of abnormal meiosis, that lead to chromosome imbalances, translated into birth defects and severe conditions.

Mouse females carrying the mutant were also born with less egg cells, so that they entered prematurely in menopause.

The team randomly provoked mutations in the mouse genome and then analyzed for infertility the resulting mice. DNA analysis of the sterile males pointed out the mutant inducing infertility.

The team thinks this type of dominant effect resembles the infertility type found in humans. "People have been sequencing genes in humans, including the Dmc1 gene, to try and associate changes in gene sequences with infertility," said Schimenti. "There have been occasional reports that in some patients, a sequence change in this or other meiosis genes might cause a dominant defect in function, but until now there has been no definitive proof."

"Mouse models will be critical in distinguishing between those DNA sequence changes that are benign in humans versus those that disrupt sperm or egg production. The researchers are engaged in a project to identify ultimately all the genes needed for fertility in mice and apply this information to the human situation", he said.