Doctors are seeing an alarming increase in cases of a specific genital malformation in male babies, and new research suggests environmental factors might be at play.

The malformation is known as hypospadias, where the opening of the urethra is not at the tip of the penis, but on the underside of the organ.

In the study, scientists identified a direct link between hypospadias tissue samples and the presence of epigenetic alterations — changes to the molecular factors and processes around DNA that determine how genes behave.

“Previous researchers have done extensive analyses and not found any kind of genetic DNA sequence mutations that correlate with the presence of the disease, so there has always been a big question mark regarding where it comes from,” explained senior study author Michael Skinner, a professor of biology at Washington State University.

“Our study shows the etiology of the disease is environmentally driven through epigenetics, rather than a result of changes to the DNA sequence,” he said in a university news release. “It gives us a clearer picture of what is going on.”

Incidents of this malformation have increased by 11.5% in recent decades.

This research could ultimately lead to earlier detection and better clinical management this genital defect, the study authors said.

What happens next is uncertain, but researchers pointed to one potential path. It could be identifying a specific epigenetic biomarker that doctors could collect with a simple cheek swab from the parents of a baby to determine the likelihood that a newborn will develop the defect.

“This is not so far-fetched,” Skinner said. “We have identified these types of biomarkers for other diseases. Early detection means they could do clinical management sooner, which could result in fewer complications for the baby and more peace of mind for the parents.”

Researchers don’t know what specific environmental factors are leading to hypospadias. They said it’s possible that it’s a synthetic estrogen called diethylstilbestrol (DES) that was prescribed to pregnant women in the late 1950s and early 1960s to prevent miscarriages and premature births. Affected babies would pass down this likelihood to future generations.

“There was never really evidence that it helped with pregnancy, but after the fact doctors started to find severe developmental effects from the drug on babies. Hypospadias were one of the issues,” Skinner said.

“Unfortunately, because epigenetic changes caused by drugs like this and other environmental toxicants are epigenetically heritable, they are often passed down from one generation to the next after they are contracted,” he explained. “Over time, the detrimental effects can persist and spread.”

The findings were published recently in the journal Science Reports.

More information

The U.S. Centers for Disease Control and Prevention has more on hypospadias.

SOURCE: Washington State University, news release, Jan. 18, 2023