Scientists discover sperm energy switch, opening path to male birth control

Researchers identify a sperm energy switch

Scientists have discovered the molecular mechanism that rapidly boosts sperm energy just before fertilization. The finding, published in the Proceedings of the National Academy of Sciences, could lead to new infertility treatments and nonhormonal male contraceptives.

"Sperm metabolism is special since it's only focused on generating more energy to achieve a single goal: fertilization," said senior author Melanie Balbach, an assistant professor at Michigan State University. Before ejaculation, sperm are in a low-energy state. Once inside the female reproductive tract, they must quickly ramp up energy production to swim forcefully and prepare to fuse with an egg.

Tracking the fuel for fertilization

Balbach's team, with collaborators from Memorial Sloan Kettering Cancer Center and the Van Andel Institute, developed a method to trace how sperm process glucose for fuel. They mapped the sugar's chemical pathway inside the cell, comparing inactive sperm to activated ones.

"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."

Using MSU's Mass Spectrometry and Metabolomics Core, the researchers assembled a detailed picture of the multi-step, high-energy process sperm use. They identified clear metabolic differences between the two states.

A key enzyme controls the switch

The study pinpointed a specific enzyme, aldolase, as playing a crucial role in converting glucose into usable energy. The research also revealed that sperm initially draw on internal energy reserves before switching to external fuel sources like glucose.

Certain enzymes were found to act as regulators, directing glucose through metabolic pathways and controlling the efficiency of energy production. This gives scientists a clear target for potential intervention.

Balbach plans to continue investigating how sperm use different fuels, including fructose. This research may affect several areas of reproductive health.

Potential for new contraceptives and treatments

The discovery has two major potential applications: treating infertility and creating new contraceptives. Infertility affects about one in six people worldwide, and understanding sperm metabolism could lead to better diagnostic tools and assisted reproductive technologies.

More immediately, the findings support the development of nonhormonal male birth control. Most current efforts focus on stopping sperm production, which is not immediate and often uses hormones with side effects.

Balbach's work suggests an alternative: temporarily disabling sperm function by targeting their metabolism. "One option is to explore if one of our 'traffic-control' enzymes could be safely targeted as a nonhormonal male or female contraceptive," she said.

This approach could offer several advantages over existing methods:

• It would be nonhormonal, avoiding related side effects.
• It could provide on-demand, temporary infertility when desired.
• It gives men more agency and could reduce reliance on female hormonal birth control.

Next steps for the research

The immediate next step is to see if these findings translate to human sperm. "Better understanding the metabolism of glucose during sperm activation was an important first step," Balbach said. "Now we're aiming to understand how our findings translate to other species, like human sperm."

Balbach's earlier work at Weill Cornell Medicine showed that blocking a critical sperm enzyme caused temporary infertility in mice, highlighting the feasibility of this approach. The new research provides the specific metabolic map needed to develop targeted inhibitors.

"Right now, about 50% of all pregnancies are unplanned," Balbach noted. "I'm excited to see what else we can find and how we can apply these discoveries." The research was supported by the National Institute of Child Health and Human Development.