A Gene Linked to Male Infertility Has Been Discovered, and It May Account for Some of the 50 Percent of Unexplained Cases

Scientists have discovered a gene linked to male infertility, which they believe could account for some of the 50 percent of unexplained cases thought to be related to genetics.

Variants of a gene called SYCP2 could be the reason why some men struggle to conceive with their partners, according to the authors of a study published in the American Journal of Human Genetics. So far, they have pinpointed them in four men with fertility problems.

Back in 1991, a 28-year-old man who had been unable to conceive for two years and had a very low sperm count was referred to the authors of the study. The team assessed his chromosomes, and found he had what is known as a chromosomal rearrangement, where parts of the chromosome might be missing, duplicated, or moved around. This appeared to make the SYCP2 gene 20 times more active, they found.

Identifying this abnormality led the researchers to look at how the gene behaved in a lab using cells and yeast. By modeling the rearrangement in yeast, they found it appeared to trigger an issue linked with defective sperm production in mammals, they wrote in the study.

Next, they looked at whether infertile males had variants of this gene, working with scientists at the University of Münster. Compared with the general population, disruptions to SYCP2 were more common in those with fertility problems, the investigators found.

Co-author Samantha Schilit, an expert in unexplained infertility at Harvard Medical School, commented in a statement that these chromosomal problems in infertile men are rarely followed up beyond reporting a higher risk for an issue, which can lead to recurrent miscarriages.

"This work shows that a chromosomal rearrangement may also disrupt or dysregulated genes important in fertility, and therefore should be considered."

Infertility is one of the most common problems among those aged between 20 to 45 years old, affecting between 10 to 15 percent of couples. Evidence suggests doctors are unable to diagnose the source of the problem in between 40 to 72 percent of men. Of those, between 30 to 50 percent of cases are estimated to be caused by genetics, the authors wrote. "Searching for genes involved in unexplained infertility is a rich endeavor," they said.

Co-author Cynthia Morton, a medical geneticist at the Brigham and Women's Hospital, told Newsweek: "This study focuses our interest in chromosomal rearrangements that underlie infertility beyond what is typically presumed—that is, the infertility results from embryos that are chromosomally unbalanced and may lead to miscarriage."

Morton, whose laboratory has had a longstanding interest in structural rearrangements of human chromosomes that underlie clinical disorders, said: "It brings emphasis to the fact that structural rearrangements in chromosomes may contribute to infertility by dysregulating gene expression of genes with a role in gametogenesis," or the creation of sperm.

More work needs to be done to validate the role of SYCP2 male infertility. This would be strengthened by finding more males with genomic variants in SYCP2, she said. The team envisions SYCP2 one day being included in genetic screenings for males to identify the genetic basis of infertility.

"A diagnosis can be therapeutic in itself -- even if there isn't something that can be done to correct it. It ends the search for the underlying issue and opens the door for enrolling in clinical trials," said Morton. "And I believe there is good reason to be optimistic; we now have better tools for discovery and can begin on the path toward therapy."

This article was updated to clarify statistics on male infertility.