Overview: A Molecular Switch Powers the Final Sprint
Michigan State University scientists have pinpointed the molecular switch that supercharges sperm for their final sprint to an egg. The discovery sheds light on how sperm shift from a resting, low-energy state to high-speed, high-energy power, a transformation essential for fertilization. The research holds promise for advancing infertility treatments and could pave the way for safe, nonhormonal male contraceptives.
Why Sperm Energy Matters
“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilization,” notes Melanie Balbach, assistant professor in the Department of Biochemistry and Molecular Biology and senior author of the study. Before ejaculation, mammalian sperm are quiet, conserving energy. Once they enter the female reproductive tract, they undergo rapid changes that enable vigorous swimming and membrane remodeling necessary to encounter and fertilize an egg.
Balbach has long studied sperm metabolism. In 2023, she helped uncover that inhibiting a key sperm enzyme could render mice temporarily infertile, raising the prospect of nonhormonal male birth control. The current work continues that thread, revealing how metabolism adapts to meet the energy demands of fertilization.
Tracking the Fuel: Glucose Metabolism in Activated Sperm
To understand how sperm rewire their energy systems, Balbach’s team collaborated with researchers at Memorial Sloan Kettering Cancer Center and the Van Andel Institute. They developed a technique to track how sperm take up and burn glucose—an essential fuel—as they transition from dormant to active states.
“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.”
The study leveraged MSU’s Mass Spectrometry and Metabolomics Core to map the high-energy, multistep process that culminates in fertilization. The researchers identified that the enzyme aldolase helps sperm convert glucose into usable energy and that sperm can also utilize onboard molecular fuel as they embark on their journey. They also uncovered metabolic “traffic regulators”—enzymes that modulate the flow of glucose to keep energy production in sync with the sperm’s needs.
Implications: From Infertility Treatment to Contraception
The findings could influence multiple aspects of reproductive health. Infertility affects roughly one in six people globally, and a deeper understanding of sperm metabolism may improve assisted reproduction techniques and diagnostic tools for infertility. Beyond treatment, the research opens the door to nonhormonal contraception strategies that offer on-demand male infertility with fewer side effects than traditional hormone-based 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 potential path is to determine whether a traffic-control enzyme could be safely targeted for nonhormonal contraception in men or women.
A Path Forward: Broadening the Scope of Sperm Metabolism Research
Traditional male contraceptives have focused on blocking sperm production, but these options can be inflexible and hormone-driven. The current research suggests a different strategy: targeting metabolic pathways active during activation to achieve on-demand fertility control with minimal side effects. As the team pursues translation to human biology, the work may also inform infertility diagnostics and new treatments for metabolic or reproductive disorders.
What’s Next
Balbach and colleagues plan to investigate how sperm utilize alternative energy sources, such as fructose, to sustain energy needs during the fertilization window. They also intend to explore the applicability of their findings across species to determine whether the same metabolic switches operate in human sperm. The ultimate aim is to translate metabolic insights into practical clinical tools—both for helping people conceive and for offering safe, nonhormonal birth control options.
“Right now, about 50% of all pregnancies are unplanned, and this would give men additional options and agency in their fertility,” Balbach said. “I’m excited to see what else we can find and how we can apply these discoveries.”
