Unlocking the energy behind fertilisation
Researchers at Michigan State University have identified the molecular mechanism that powers sperm with a final burst of energy just before fertilisation. This discovery sheds light on how sperm switch from a low-energy state in the male reproductive tract to a high-energy, propulsion-ready state once they reach the egg, a transition that is essential for successful fertilisation.
“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilisation,” says Melanie Balbach, an assistant professor in the Department of Biochemistry and Molecular Biology and the senior author of the study. “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.”
From discovery to potential therapies
Balbach’s earlier work as a postdoctoral researcher hinted at the therapeutic potential of dampening sperm metabolism. In that work, temporarily inhibiting a crucial sperm enzyme rendered mice infertile, suggesting a nonhormonal approach to male contraception. The new research builds on that groundwork by detailing how sperm produce the energy necessary to complete the journey to fertilisation.
Tracking metabolism in action
The team collaborated with Memorial Sloan Kettering Cancer Center and the Van Andel Institute to develop a technique that traces glucose metabolism in sperm. Glucose acts as fuel, and following its metabolic trail revealed stark contrasts between dormant and activated sperm. Balbach describes the method as “painting the roof of a car bright pink and following that car through traffic using a drone,” illustrating how activated sperm move through a metabolic landscape that favours speed and precision.
Using MSU’s Mass Spectrometry and Metabolomics Core, the researchers mapped the high-energy, multistep process sperm undergo to reach fertilisation. They found that an enzyme called aldolase helps convert glucose into usable energy and that sperm also exploit stored molecular fuel as they begin their journey. Additional enzymes act as traffic controllers, regulating glucose flow and coordinating energy production.
Implications for fertility and contraception
The findings have broad implications. By understanding how sperm use different fuels—including glucose and fructose—to sustain energy, scientists may improve assisted fertility techniques and diagnostics for infertility, which affects roughly one in six people globally. Moreover, the research points toward safer, nonhormonal contraception options. While many male contraceptives target sperm production and use hormonal approaches that can cause significant side effects, this metabolism-centric strategy could enable on-demand contraception with fewer adverse effects.
Balbach emphasizes the translational potential: “One option is to see if one of our ‘traffic-control’ enzymes could be safely targeted as a nonhormonal male or female contraceptive.” She envisions translating these insights to humans and other species, broadening the impact of the discovery beyond the initial animal models.
Looking ahead
As infertility remains a growing concern—affecting about 16% of couples worldwide—advances in understanding sperm energy use offer promise for both fertility treatments and contraception. The next steps include validating whether the same metabolic switches operate in human sperm and evaluating the safety and efficacy of targeting sperm metabolism in clinical contexts. If successful, this line of research could provide new options for people seeking to start a family and those seeking reliable nonhormonal birth control.
