Researchers have traced how sperm rapidly shift from a dormant to an energy-charged state during their journey to fertilize an egg.
Researchers at Michigan State University have identified a molecular “switch” that boosts sperm energy during their final push to reach an egg. This breakthrough could transform how infertility is treated and open the door to new, nonhormonal options for male contraception.
“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 paper.
Before ejaculation, sperm in mammals remain in a low-energy, inactive state. Once released, they begin their journey through the female reproductive tract, where they experience a series of transformations that prepare them for fertilization. These changes include faster, more powerful swimming motions and modifications to the membranes that will eventually come into contact with 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,” said Balbach, who, in 2023, brought her pioneering science on sperm metabolism to MSU.
As a postdoctoral researcher at Weill Cornell Medicine, Balbach drove the headline-making discovery that the inhibition of a crucial sperm enzyme rendered mice temporarily infertile. This breakthrough raised the exciting potential for a nonhormonal male birth control.
Unraveling How Sperm Fuel Themselves
Metabolism is similarly essential for sperm function, and while scientists knew that behavioral changes prior to fertilization required a large amount of energy, they weren’t sure how sperm adjusted to meet the demand — until now.
Teaming up with scientists at Memorial Sloan Kettering Cancer Center and the Van Andel Institute, Balbach’s group created a special technique that allowed them to track the metabolism of glucose, which sperm take up from their environment and use as a sort of fuel.
By tracing the chemical journey of glucose within sperm, they observed key differences between dormant and active specimens.
“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 added.
By leveraging facilities such as MSU’s Mass Spectrometry and Metabolomics Core, the study paints a fuller picture of the high-energy, multistep process required for sperm to reach their goal of fertilization.
This includes the discovery that a particular enzyme called aldolase helps sperm convert glucose into energy and that sperm even utilize molecular fuel that they already have on board when they begin their trek.
The experiments also revealed how some enzymes regulate the flow of glucose like traffic controllers.
Implications for Fertility and Contraception
Looking ahead, Balbach will continue to explore how sperm use a variety of fuel sources like glucose and fructose to meet their energy needs. This research can potentially impact a number of reproductive health issues.
With one in six individuals impacted by infertility globally, Balbach sees the analysis of sperm metabolism as an especially promising research direction for improving both assisted fertility techniques and the diagnosis of infertility in patients.
This work can also help develop new methods of contraception like nonhormonal birth control.
“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.
Rethinking Male Contraceptives
The traditional development of male contraceptives has focused on blocking sperm at their creation. This approach, however, comes with notable drawbacks. The process of becoming infertile is far from on demand, and such contraceptives are commonly hormone-based, leading to many severe side effects.
The latest findings from Balbach and her collaborators are paving the way for a sperm metabolism-centered solution to these challenges: an inhibitor-based, nonhormonal method of contraception that would allow for on-demand male infertility with little to no side 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.”
Reference: “Sperm meet the elevated energy demands to attain fertilization competence by increasing flux through aldolase” by Sara Violante, Aye Kyaw, Lana Kouatli, Kaushik Paladugu, Lauren Apostolakis, Macy Jenks, Amy Johnson, Ryan D. Sheldon, Douglas Whitten, Anthony L. Schilmiller, Pablo E. Visconti, Justin R. Cross, Lonny R. Levin, Jochen Buck and Melanie Balbach, 24 September 2025, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2506417122
The Michigan State University-led project was supported by funding from the National Institute of Child Health and Human Development.
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3 Comments
If they could get that into the losers that only breed and sponge of the system.
Feminists are not going to be happy when they find out they can’t trap men anymore.
Very probably, every time – people think to accomplish something, they don’t see what will actually happen. usually, it is something they could have to understood if they had stopped with the instant tunnel-vision for two seconds and used their brains. But humans have this very bad habit.
Maybe AI’s true boon will be to say “unh-uh!” every time nitwits have a new idea.
Don’t laugh, there’s a good business here and I’m sure it’ll become the norm.