Unlocking Male Fertility: Scientists Identify Molecular Switch Controlling Sperm Energy
A newly discovered molecular mechanism controlling sperm energy levels could pave the way for both improved fertility treatments and a new generation of non-hormonal male contraceptives, according to research from Michigan State University. The study, published in , in the Proceedings of the National Academy of Sciences, details how sperm rapidly shift into high gear as they journey to fertilize an egg, and identifies a key enzyme involved in this process.
For decades, scientists have known that sperm require a significant energy boost to navigate the female reproductive tract and successfully fertilize an egg. However, the precise biochemical steps involved in this energy surge remained largely unknown. “Sperm metabolism is special since it’s only focused on generating more energy to achieve a single goal: fertilization,” explains Melanie Balbach, an assistant professor in the Department of Biochemistry and Molecular Biology at Michigan State University and senior author of the study.
Before ejaculation, sperm exist in a relatively dormant, low-energy state. Once released into the female reproductive tract, they undergo a dramatic transformation, increasing their swimming speed and adjusting their outer membranes to prepare for egg interaction. This rapid shift demands a substantial increase in energy production.
Mapping the Fuel Source
Balbach’s team, collaborating with researchers at Memorial Sloan Kettering Cancer Center and the Van Andel Institute, developed a novel method to track how sperm process glucose – a sugar absorbed from their surroundings and used as fuel. By mapping the chemical pathway of glucose within sperm cells, they were able to pinpoint key differences between inactive and activated sperm.
“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.” This analogy illustrates how the team was able to visualize and understand the complex metabolic processes occurring within the sperm.
Using advanced technologies at MSU’s Mass Spectrometry and Metabolomics Core, the researchers constructed a detailed picture of the multi-step, high-energy process sperm rely on to achieve fertilization.
Aldolase: A Key Regulator of Sperm Metabolism
The study identified the enzyme aldolase as playing a crucial role in converting glucose into usable energy for sperm. Researchers also discovered that sperm utilize pre-existing internal energy reserves at the beginning of their journey. The research highlighted the role of other enzymes that act as “traffic controllers,” regulating the flow of glucose through metabolic pathways and influencing the efficiency of energy production.
Balbach’s earlier work, conducted at Weill Cornell Medicine, demonstrated that inhibiting a critical sperm enzyme could temporarily induce infertility in mice. This finding provided early evidence for the potential of a non-hormonal male contraceptive approach. She brought this pioneering research on sperm metabolism to MSU in .
Implications for Infertility and Contraception
Infertility affects approximately one in six individuals globally. Balbach believes that a deeper understanding of sperm metabolism could lead to improved diagnostic tools and more effective assisted reproductive technologies. The findings also hold promise for the development of new contraceptive strategies, particularly those that avoid the use of hormones.
“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. She suggests that targeting one of the “traffic-control” enzymes could potentially lead to a safe and reversible non-hormonal contraceptive option for both men and women.
Current male contraceptive efforts largely focus on reducing sperm production, a strategy that doesn’t offer immediate, on-demand infertility and often relies on hormones with potential side effects. Balbach’s research proposes an alternative: temporarily disabling sperm function through a non-hormonal inhibitor, minimizing unwanted effects.
“Right now, about 50% of all pregnancies are unplanned, and this would give men additional options and agency in their fertility,” Balbach stated. “Likewise, it creates freedom for those using female birth control, which is hormone-based and highly prone to side effects.”
Balbach’s team plans to continue investigating how sperm utilize different fuel sources, including glucose and fructose, to meet their energy demands. This ongoing research could have broad implications for reproductive health.
Why This Matters
- Sperm require a dramatic energy boost to successfully fertilize an egg.
- Scientists have identified how sperm utilize glucose to power this surge, revealing the fuel source behind their rapid transformation.
- This discovery enhances our understanding of reproductive biology and could lead to improved infertility treatments and innovative, non-hormonal birth control options.
The research was supported by the National Institute of Child Health and Human Development.