News | Michigan State University Identifies Sperm ‘Energy Switch,’ Advancing Male Contraception and Infertility Treatment
Scientists at Michigan State University (MSU) have identified a key molecular ‘switch’ that enables sperm to sprint toward the egg. The discovery may reshape infertility treatment and pave the way for safe, nonhormonal male contraceptives.
‘Sperm metabolism is very unique—its sole purpose is to provide energy for fertilization,’ said lead researcher Dr. Melanie Balbach, assistant professor in MSU’s Department of Biochemistry and Molecular Biology.
From ‘Dormant’ to ‘Full Speed’: The Key Mechanism in Sperm Energy Conversion
Before ejaculation, mammalian sperm remain in a low-energy state. After ejaculation, they gradually activate in the female reproductive tract, begin beating vigorously, and modify their cell membranes in preparation for penetrating the egg.
Balbach explained: ‘This rapid shift from low to high energy occurs not only in sperm but in many cell types. Sperm are an ideal model for studying this metabolic reprogramming.’
Before joining MSU, Balbach gained attention for groundbreaking research during her postdoctoral work at Weill Cornell Medicine. She found that inhibiting a key sperm enzyme caused reversible, temporary infertility in mice, an important milestone in developing nonhormonal male contraception.
Tracking How Sperm ‘Fuel Up’: A New Metabolic Tracing Technique
To determine how sperm accelerate before fertilization, the MSU team collaborated with Memorial Sloan Kettering Cancer Center and Van Andel Institute to develop an advanced technique for tracking glucose metabolism.
By tracing the chemical path of glucose in sperm, the researchers clearly observed major differences between resting and active sperm.
Balbach used an analogy: ‘It is like painting a car roof pink and using a drone to track its route through traffic. In activated sperm, this “pink car” not only travels faster but takes different roads, and we can even see where it tends to become stuck at “intersections.”’
Using MSU’s mass spectrometry and metabolomics core facilities, the team mapped the high-energy, multistep metabolic pathway sperm need as they move toward the egg. One key finding was that an enzyme called **aldolase** plays a central role in helping sperm convert glucose into energy. The study also showed that sperm carry some internal energy reserves when they begin their journey.
The team also found that certain enzymes act like ‘traffic controllers,’ regulating glucose flow through sperm metabolism to maintain a steady energy supply.
New Directions for Infertility Treatment and Contraceptive Development
Balbach’s team will next explore how sperm use different energy sources, such as glucose and fructose, to meet their needs. The work may improve assisted reproductive technology (ART) and infertility diagnosis while identifying new targets for nonhormonal contraception.
‘About one in six people worldwide is affected by infertility,’ Balbach said. ‘Studying sperm metabolism gives us a way to improve fertility and design new contraceptive strategies.’
Most male contraceptive research currently focuses on blocking sperm production. These methods act slowly, cannot be controlled on demand, and often rely on hormones with significant side effects. Balbach’s team instead proposes inhibiting sperm metabolic enzymes for reversible, nonhormonal, on-demand contraception—with theoretically few side effects.
Balbach said: ‘About 50% of pregnancies worldwide are currently unintended. Giving men more safe, controllable contraceptive options would promote gender equality and relieve women of the long-term burden of hormonal contraception.’
The findings were published in Proceedings of the National Academy of Sciences and funded by the National Institute of Child Health and Human Development (NICHD).
News | Michigan State University Identifies Sperm ‘Energy Switch,’ Advancing Male Contraception and Infertility Treatment
News | Michigan State University Identifies Sperm ‘Energy Switch,’ Advancing Male Contraception and Infertility Treatment
Scientists at Michigan State University (MSU) have identified a key molecular ‘switch’ that enables sperm to sprint toward the egg. The discovery may reshape infertility treatment and pave the way for safe, nonhormonal male contraceptives.
‘Sperm metabolism is very unique—its sole purpose is to provide energy for fertilization,’ said lead researcher Dr. Melanie Balbach, assistant professor in MSU’s Department of Biochemistry and Molecular Biology.
From ‘Dormant’ to ‘Full Speed’: The Key Mechanism in Sperm Energy Conversion
Before ejaculation, mammalian sperm remain in a low-energy state. After ejaculation, they gradually activate in the female reproductive tract, begin beating vigorously, and modify their cell membranes in preparation for penetrating the egg.
Balbach explained: ‘This rapid shift from low to high energy occurs not only in sperm but in many cell types. Sperm are an ideal model for studying this metabolic reprogramming.’
Before joining MSU, Balbach gained attention for groundbreaking research during her postdoctoral work at Weill Cornell Medicine. She found that inhibiting a key sperm enzyme caused reversible, temporary infertility in mice, an important milestone in developing nonhormonal male contraception.
Tracking How Sperm ‘Fuel Up’: A New Metabolic Tracing Technique
To determine how sperm accelerate before fertilization, the MSU team collaborated with Memorial Sloan Kettering Cancer Center and Van Andel Institute to develop an advanced technique for tracking glucose metabolism.
By tracing the chemical path of glucose in sperm, the researchers clearly observed major differences between resting and active sperm.
Balbach used an analogy: ‘It is like painting a car roof pink and using a drone to track its route through traffic. In activated sperm, this “pink car” not only travels faster but takes different roads, and we can even see where it tends to become stuck at “intersections.”’
Using MSU’s mass spectrometry and metabolomics core facilities, the team mapped the high-energy, multistep metabolic pathway sperm need as they move toward the egg. One key finding was that an enzyme called **aldolase** plays a central role in helping sperm convert glucose into energy. The study also showed that sperm carry some internal energy reserves when they begin their journey.
The team also found that certain enzymes act like ‘traffic controllers,’ regulating glucose flow through sperm metabolism to maintain a steady energy supply.
New Directions for Infertility Treatment and Contraceptive Development
Balbach’s team will next explore how sperm use different energy sources, such as glucose and fructose, to meet their needs. The work may improve assisted reproductive technology (ART) and infertility diagnosis while identifying new targets for nonhormonal contraception.
‘About one in six people worldwide is affected by infertility,’ Balbach said. ‘Studying sperm metabolism gives us a way to improve fertility and design new contraceptive strategies.’
Most male contraceptive research currently focuses on blocking sperm production. These methods act slowly, cannot be controlled on demand, and often rely on hormones with significant side effects. Balbach’s team instead proposes inhibiting sperm metabolic enzymes for reversible, nonhormonal, on-demand contraception—with theoretically few side effects.
Balbach said: ‘About 50% of pregnancies worldwide are currently unintended. Giving men more safe, controllable contraceptive options would promote gender equality and relieve women of the long-term burden of hormonal contraception.’
The findings were published in Proceedings of the National Academy of Sciences and funded by the National Institute of Child Health and Human Development (NICHD).
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