This breakthrough could finally unlock male birth control

“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilization,” said Melanie Balbach, an assistant professor in the Department of Biochemistry and Molecular Biology and senior author of the study.

Before ejaculation, mammalian sperm remain in a low energy state. Once inside the female reproductive tract, they rapidly transform. They begin swimming more forcefully and adjust the outer membranes that will eventually interact with the egg. These changes demand a sudden and significant rise in energy production.

“Many types of cells undergo this rapid switch from low to high energy states, and sperm are an ideal way to study such metabolic reprogramming,” Balbach said. She joined MSU in 2023 to expand her pioneering work on sperm metabolism.

Tracking the Fuel That Powers Fertilization

Earlier in her career at Weill Cornell Medicine, Balbach helped show that blocking a critical sperm enzyme caused temporary infertility in mice. That discovery highlighted the possibility of nonhormonal male birth control.

Although scientists understood that sperm require large amounts of energy to prepare for fertilization, the exact mechanism behind this surge remained unclear until now.

Working with collaborators at Memorial Sloan Kettering Cancer Center and the Van Andel Institute, Balbach’s team developed a method to follow how sperm process glucose, a sugar they absorb from their surroundings and use as fuel.

By mapping glucose’s chemical path inside the cell, the researchers identified clear differences between inactive sperm and those that had been activated.

“You can think of this approach like painting the roof of a car bright pink and then following that car through traffic using a drone,” Balbach explained.

“In activated sperm, we saw this painted car moving much faster through traffic while preferring a distinct route and could even see what intersections the car tended to get stuck at,” she said.

Using resources such as MSU’s Mass Spectrometry and Metabolomics Core, the team assembled a detailed picture of the multi step, high energy process sperm rely on to achieve fertilization.

Aldolase and the Control of Sperm Metabolism

The study found that an enzyme known as aldolase plays a key role in converting glucose into usable energy. Researchers also learned that sperm draw on internal energy reserves they already carry when their journey begins.

In addition, certain enzymes act like regulators, directing how glucose moves through metabolic pathways and influencing how efficiently energy is produced.

Balbach plans to continue investigating how sperm rely on different fuel sources, including glucose and fructose, to meet their energy demands. This line of research may affect multiple areas of reproductive health.

Implications for Infertility and Nonhormonal Birth Control

Infertility affects about one in six people worldwide. Balbach believes that studying sperm metabolism could lead to better diagnostic tools and improved assisted reproductive technologies.

The findings may also support the development of new contraceptive strategies, particularly nonhormonal approaches.

“Better understanding the metabolism of glucose during sperm activation was an important first step, and now we’re aiming to understand how our findings translate to other species, like human sperm,” Balbach said.

“One option is to explore if one of our ‘traffic-control’ enzymes could be safely targeted as a nonhormonal male or female contraceptive,” she added.

Most efforts to create male contraceptives have focused on stopping sperm production. That strategy has drawbacks. It does not provide immediate, on demand infertility, and many options rely on hormones that can cause significant side effects.

Balbach’s latest work suggests an alternative. By targeting sperm metabolism with an inhibitor based, nonhormonal approach, it may be possible to temporarily disable sperm function when desired while minimizing unwanted effects.

“Right now, about 50% of all pregnancies are unplanned, and this would give men additional options and agency in their fertility,” Balbach said. “Likewise, it creates freedom for those using female birth control, which is hormone-based and highly prone to side effects.

“I’m excited to see what else we can find and how we can apply these discoveries.”

Why This Matters

• Sperm must dramatically boost their energy levels to complete the demanding journey to an egg and achieve fertilization.
• Scientists have now uncovered how sperm tap into glucose in their surroundings to power this surge, revealing the fuel source behind their rapid transformation.
• This discovery deepens our understanding of reproductive biology and could open the door to better infertility treatments and innovative, nonhormonal birth control options.

The research was published in the Proceedings of the National Academy of Sciences and supported by the National Institute of Child Health and Human Development.