Scientists Find Sperm’s Energy Switch for Egg Sprint

Researchers at Michigan State University have identified the molecular switch that drives sperm into a high-speed sprint toward an egg. The team tracked how sperm pull glucose from their surroundings to fuel this final burst, revealing a step-by-step process that flips dormant cells into active ones. This finding, detailed in recent work, could lead to better infertility care and new birth control methods.

Background

Sperm need a big energy boost right before they reach an egg to fertilize it. For years, scientists knew this final stage demanded a lot of power, but they did not know exactly how sperm made the switch from low to high energy. Teams have studied sperm metabolism before, but gaps remained in understanding the quick changes that happen just before fertilization.

Melanie Balbach, an assistant professor in the Department of Biochemistry and Molecular Biology at Michigan State University, led the effort. She moved her lab to the university in 2023 after earlier work at Weill Cornell Medicine. There, she found that blocking a key sperm enzyme made mice temporarily unable to father offspring. That result hinted at possibilities for birth control without hormones.

Balbach's group worked with scientists from Memorial Sloan Kettering Cancer Center and the Van Andel Institute. They focused on glucose, the main fuel sperm grab from the female reproductive tract. Sperm also carry some fuel inside them from the start of their journey. Past studies showed sperm behavior changes demand energy, but the exact path of that energy stayed unclear until this research.

One in six people worldwide deals with infertility, and male factors play a role in half of those cases. Better grasp of sperm energy use could help doctors spot problems earlier and improve treatments like in vitro fertilization.

Key Details

The team built a new method to follow glucose inside sperm cells. They used a type of tracking that acts like marking a car with bright paint and watching it move through traffic from above. This let them see how glucose flows differently in resting sperm compared to active ones.

In active sperm, glucose moves faster along a specific path. The researchers found that an enzyme named aldolase plays a central role. It breaks down glucose to release energy for the sperm's dash. Other enzymes work like traffic controllers, guiding the fuel flow and preventing jams in the process.

The Tracking Technique

To watch this in real time, the group fed sperm a special version of glucose marked with carbon-13 isotopes. They pulled sperm from mouse epididymis, a storage area, and placed them in lab conditions that mimic the female tract—some setups kept sperm dormant, others triggered activation.

Using Michigan State University's Mass Spectrometry and Metabolomics Core, they mapped the glucose path. Dormant sperm used glucose slowly. Activated ones ramped up, burning fuel in a multi-step chain. They even tapped into stored energy onboard from earlier stages.

“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 said. “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.”

This multi-step process ensures sperm save energy until the last moment, then unleash it all for the sprint. Aldolase stands out as the main converter, turning sugar into the power burst needed.

What This Means

This discovery maps out how sperm meet their huge energy needs at the key moment of fertilization. It could change how doctors handle infertility. For example, tests that check sperm metabolism might predict fertility better than standard counts. Assisted reproduction could improve by mimicking these energy steps in labs.

The work also opens paths to nonhormonal birth control for men. Earlier findings from Balbach showed enzyme blocks stop fertility in mice without side effects. Now, with details on aldolase and traffic enzymes, researchers can test safe ways to target them. The team plans to check if these steps work the same in human sperm and other species.

“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilization,” said Balbach.

Future studies will look at other sugars like fructose that sperm use. This could help with female contraceptives too, if similar controls appear in eggs. Globally, infertility affects millions, and male options for birth control have lagged behind female ones. Reliable, reversible pills for men remain absent from markets.

The research highlights sperm as a model for other cells that switch energy states fast, like in cancer or muscle cells. But the focus stays on reproduction. With infertility rates steady or rising, these insights come at a needed time. Balbach's lab will push to translate mouse results to humans, testing enzyme targets for safety and effect.

Experts note that while mouse sperm share traits with human ones, full proof needs human trials. Still, the clear metabolic map gives a strong start. Labs worldwide may build on this to refine fertility diagnostics and contraception designs. Patients facing infertility could see new tools soon, and couples seeking control over family planning might gain fresh choices.