Unlocking the energy behind fertilisation
Scientists have identified a molecular “switch” that powers sperm energy just before fertilisation, a breakthrough that could lead to innovative fertility therapies and safer, nonhormonal male contraceptives. The discovery, led by researchers at Michigan State University, centers on how sperm switch from a low-energy state to the intense energy burst required to reach and fertilize the egg.
“Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilisation,” explained Melanie Balbach, an assistant professor in the Department of Biochemistry and Molecular Biology and the senior author of the study. Before ejaculation, mammalian sperm sit in a low-energy state. Once inside the female reproductive tract, they undergo rapid metabolic changes that enable vigorous swimming and prepare their membranes for interaction with the egg.
Balbach highlighted that many cell types undergo rapid high-energy transitions, and sperm offer a unique opportunity to study this metabolic reprogramming in action. The research provides new insight into how a final energy boost is generated to meet the demanding task of fertilisation.
From discovery to potential contraception and therapies
In a pivotal earlier finding, Balbach, then a postdoctoral researcher at Weill Cornell Medicine, showed that inhibiting a crucial sperm enzyme could temporarily render mice infertile. This hinted at a promising nonhormonal route to male birth control. The latest work extends this line of inquiry by mapping how sperm fuel their journey in real time and identifying key points that could be targeted in humans.
To study glucose metabolism in sperm, the team collaborated with Memorial Sloan Kettering Cancer Center and the Van Andel Institute. They developed a technique to track glucose usage as sperm activate. Glucose acts as fuel, and tracing its path revealed distinct contrasts between dormant and active sperm, illuminating the steps that convert simple sugars into the energy needed for fertilisation.
Balbach used a vivid analogy: “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. In activated sperm, we saw this painted car moving much faster through traffic, preferring a distinct route and even showing where it might get stuck.” The team leveraged MSU’s Mass Spectrometry and Metabolomics Core to construct a detailed map of the high-energy, multistep process sperm undergo to reach fertilisation.
The molecular players and the path forward
The researchers identified aldolase, a key enzyme that helps sperm convert glucose into usable energy, along with other enzymes that regulate glucose flow like traffic controllers. They also found that sperm tap into stored molecular fuel as they commence their journey, illustrating a coordinated energy strategy rather than a single-step reaction.
Balbach intends to continue exploring how different fuels, including glucose and fructose, sustain energy during activation. With infertility affecting about one in six people globally, these findings could enhance assisted reproduction techniques and diagnostics. Importantly, traditional male contraceptives largely target sperm production and hormones, which can cause significant side effects. A metabolism-centered approach offers a potential path to on-demand, nonhormonal contraception with fewer adverse effects.
Implications for fertility and contraception
“Better understanding glucose metabolism during sperm activation is a crucial first step,” Balbach said. “We aim to translate these findings across species, including human sperm, to evaluate whether one of our ‘traffic-control’ enzymes could be safely targeted as a nonhormonal contraceptive for men or women.”
As the global demand for safer, more controllable fertility options grows, this research signals a shift toward targeting the metabolic engine of sperm. If validated in humans, therapies could improve infertility treatments and enable new, hormone-free contraception that offers greater choice and agency for people planning families.
