Michigan State University scientists are aiming to make the male fertility process easier by promoting non-hormonal based treatment. The difficulty is the sperm requiring sudden demand for energy production; before ejaculation, the sperm is in a low energy state. When it reaches the female reproductive tract, it has to swim forcefully and adjust the outer membrane that will encounter an egg.
“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,” Melanie Balbach, an assistant professor at MSU’s Department of Biochemistry and Molecular Biology, said.
The researchers at MSU developed a method to follow how sperm processes glucose, a sugar they absorb from their surroundings, to use as fuel. They also noticed how enzymes helped the sperm move. The enzyme aldolase converted glucose into usable energy.
There are also enzymes that act like regulators that influence how efficiently energy is produced and direct how glucose moves through metabolic pathways.
This experiment started from the discovery that the inhibition of a crucial sperm enzyme rendered mice temporarily infertile. Previously, due to metabolic processes going in parallel, it was difficult to identify the molecular mechanisms regulating the increase in production.
By mapping the glucose’s chemical path inside the cell, the scientists were able to identify the differences between inactive sperm and those that had been activated.
The activated sperm is similar to a car that moves faster through the traffic while favoring a distinct route and could even see what intersections the car tended to get stuck at.
Once activated, the sperm broke down glucose through a pathway called glycolysis while reducing activity in the pathway that normally uses glucose for other cellular tasks.
The glucose was first broken down into a smaller molecule called pyruvate. In the midsection of the sperm where the mitochondria reside, the pyruvate entered a series of reactions that produced large amounts of energy through oxidative phosphorylation.
In the flagellum, which lacks mitochondria, the sperm relied mainly on glycolysis to make energy. Pyruvate was then converted into lactate to help recycle important helper molecules called nicotinamide adenine dinucleotide, that glycolysis needs to continue producing energy. Some of the lactate was then released from the sperm cell.
Infertility affects one in six people worldwide. Furthermore, hormone treatments can cause significant side effects. The scientists at MSU are targeting sperm metabolism with an inhibitor-based, nonhormonal approach that minimizes these unwanted effects and offers the potential to temporarily disable sperm function when desired.
This discovery can improve the current understanding of reproductive biology and lead to better contraceptive treatments that provide men greater autonomy over their fertility. It also offers freedom for those using female birth control since hormone-based solutions are highly prone to side effects.
Advancing the science of fertility is an advantage for people who want to conceive while offering safer initiatives so that reproduction can occur on a couple’s own terms.
