Researchers have pinpointed the molecular “switch” that supercharges sperm for their final sprint to an egg. This groundbreaking discovery could reshape infertility treatments and pave the way for safe, nonhormonal male contraceptives.

“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilization,” says Melanie Balbach, an assistant professor in the biochemistry and molecular biology department at Michigan State University and senior author of the study.

### From Low-Energy State to High Performance

Before ejaculation, mammalian sperm rest in a low-energy state. Afterward, as they swim through the female reproductive tract, they undergo a series of changes that help them reach and fertilize an egg. These changes include swimming with quick, vigorous movements and modifications to the membranes that encounter the egg.

“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,” says Balbach, who joined MSU in 2023 with her pioneering research on sperm metabolism.

### A Breakthrough in Male Contraception Research

During her postdoctoral work at Weill Cornell Medicine, Balbach made a headline-making discovery: inhibiting a crucial sperm enzyme rendered mice temporarily infertile. This breakthrough revealed exciting potential for nonhormonal male birth control.

While metabolism is essential for sperm function, scientists previously did not fully understand how sperm adjust their energy demands prior to fertilization — until now.

### Tracking Glucose Metabolism in Sperm

Collaborating with scientists at Memorial Sloan Kettering Cancer Center and the Van Andel Institute, Balbach’s team developed a novel technique to track glucose metabolism within sperm. Glucose, which sperm absorb from their environment, acts as a critical fuel source.

By tracing glucose’s chemical journey, the researchers observed key differences between dormant and activated sperm.

“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 explains. “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.”

### Key Findings: The Role of Enzymes in Sperm Energy Conversion

The study reveals a fuller picture of the high-energy, multistep process sperm undergo to achieve fertilization. Notably, it found that an enzyme called aldolase helps sperm convert glucose into usable energy. Additionally, sperm utilize molecular fuel already on board as they start their journey.

The experiments also showed how certain enzymes act as “traffic controllers” to regulate glucose flow inside sperm cells.

### Implications for Reproductive Health

Looking ahead, Balbach aims to explore how sperm use various fuel sources, including glucose and fructose, to fulfill their energy needs.

With one in six individuals affected by infertility worldwide, Balbach believes that analyzing sperm metabolism represents a promising avenue for improving assisted fertility techniques and diagnosing infertility.

Moreover, the research could lead to innovative contraception methods, such as nonhormonal birth control.

### Toward Nonhormonal, On-Demand Male Contraception

“Better understanding the metabolism of glucose during sperm activation was an important first step,” Balbach says. “Now we want to understand how our findings translate to other species, like human sperm.”

One potential application is targeting one of the “traffic-control” enzymes to develop a safe, nonhormonal contraceptive for males or females.

Traditional male contraceptives have focused on blocking sperm production, but this approach has drawbacks. Becoming infertile is not immediate, and hormone-based contraceptives often cause severe side effects.

The latest findings pave the way for a novel sperm metabolism-centered solution: an inhibitor-based, nonhormonal contraceptive that offers on-demand male infertility with minimal side effects.

### Expanding Options and Agency in Reproductive Health

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

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

—

The research appears in the *Proceedings of the National Academy of Sciences* and was supported by the National Institute of Child Health and Human Development.
https://knowridge.com/2025/10/how-sperm-kick-into-overdrive-for-their-final-sprint/