man sitting with a condom and birth control pills

(Credit: Africa Studio/Shutterstock)

HOUSTON — Why is there no birth control pill for men? It’s an age-old question that has left guys everywhere with two options to prevent pregnancy: use condoms or get a vasectomy. Now, however, researchers from the Baylor College of Medicine believe they’ve finally found the gene that will help scientists produce reliable birth control pills for men.

Their findings published in the journal Science reveal that the gene STK33 plays a key role in creating functional sperm. Knocking out that gene, at least temporarily, could keep fertile men from impregnating their partners in a similar way that female birth control has done for decades.

“Although researchers have been investigating several strategies to develop male contraceptives, we still do not have a birth control pill for men,” says corresponding author Dr. Martin Matzuk, the director of the Center for Drug Discovery and chair of the Department of Pathology and Immunology at Baylor, in a university release. “In this study we focused on a novel approach – identifying a small molecule that would inhibit serine/threonine kinase 33 (STK33), a protein that is specifically required for fertility in both men and mice.”

Sperm and egg cell.
The findings published in the journal Science reveal that the gene STK33 plays a key role in creating functional sperm. (© vchalup – stock.adobe.com)

Using mice, the Baylor team was able to deactivate the STK33 gene, causing the creation of abnormal sperm and inducing poor sperm motility. Essentially, this left the mice sterile.

In men, scientists have found that having a mutation in this gene can cause infertility. However, a STK33 mutation does not cause any other side-effects, such as smaller than normal testis size. Simply put, a problem with STK33 doesn’t lead to visible symptoms like having smaller testicles.

“STK33 is therefore considered a viable target with minimal safety concerns for contraception in men,” adds Matzuk, who has been on faculty at Baylor for 30 years and is Baylor’s Stuart A. Wallace Chair and Robert L. Moody, Sr. Chair of Pathology and Immunology. “STK33 inhibitors have been described but none are STK33-specific or potent for chemically disrupting STK33 function in living organisms.”

So, how do you take a genetic mutation that causes sterility and turn it into a safe and reversible alternative to condoms? Study first author Dr. Angela Ku explains that the team analyzed billions of compounds in their collection that could possibly safely knock out STK33. This process led to the discovery of several compounds that could do the job. Scientists then modified these candidates to make them more stable and effective at silencing STK33.

“Among these modified versions, compound CDD-2807 turned out to be the most effective,” Ku says.

“Next, we tested the efficacy of CDD-2807 in our mouse model,” adds co-author Dr. Courtney M. Sutton, a postdoctoral fellow in the Matzuk lab. “We evaluated several doses and treatment schedules and then determined sperm motility and number in the mice as well as their ability to fertilize females.”

Microscopic image showing the effects of compound CDD-2807 on sperm motility.
Microscopic image showing the effects of compound CDD-2807 on sperm motility. (Credit: Baylor College of Medicine)

Does this mean CDD-2807 could be the first step in an actual male birth control pill? It sure looks that way. CDD-2807 was able to cross the blood-testis barrier, a boundary that protects the male body from creating anti-sperm antibodies and autoimmune diseases. It also reduced sperm motility and numbers and mice fertility at low doses. To put it bluntly, the mice had fewer “swimmers” capable of getting another mouse pregnant.

“We were pleased to see that the mice did not show signs of toxicity from CDD-2807 treatment, that the compound did not accumulate in the brain, and that the treatment did not alter testis size, similar to the Stk33 knockout mice and the men with the STK33 mutation,” Sutton says.

Perhaps the most important discovery was that the effects of CDD-2807 were completely reversible. Once the mice stopped taking CDD-2807, their sperm motility and sperm count reached fertile levels again. The team believes this could one day provide the same benefits for men everywhere.

It’s important to note that the study focuses on contraception and preventing pregnancy, not the transmission of sexually-transmitted infections. Short of avoiding sex entirely, the most effective way for men to prevent spreading or contracting STIs is through the use of condoms.

About Chris Melore

Chris Melore has been a writer, researcher, editor, and producer in the New York-area since 2006. He won a local Emmy award for his work in sports television in 2011.

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