Male infertility cure closer to reality after genetic discovery

GUANGZHOU, China — Male infertility impacts over 20 million men worldwide. It’s the cause for about half of infertility cases among couples looking to conceive a child. Researchers say male infertility often comes down to the condition of the sperm. Now, a new study is shedding light on a key mutation which damages a man’s ability to reproduce. Their findings also reveal a path to correcting the problem and restoring fertility to millions of potential parents.

In men dealing with severe infertility, malformations develop in the sperm’s flagellum, the tail which is crucial to movement. These tails become shorter, irregular, coiled, or even disappear altogether. When this happens, sperm can’t swim to reach and fertilize an egg.

Study authors from Guangzhou Women and Children’s Medical Center say many genetic mutations can lead to sperm malformations. Some of these genetic problems affect the sheath which covers the sperm and the mitochondria, which powers its movement. Others damage the acrosomal vesicle, a tiny sac that releases enzymes which allow a successful sperm to break down the outer lining of an egg cell so fertilization can begin.

Just one protein may prevent infertility in men

Researchers Na Li and Ling Sun collected sperm samples from infertile men as part of their study. They identified one individual with multiple defects that were affecting his sperm flagella. After analyzing these samples, the team discovered a specific gene mutation in a relatively unknown sperm protein — Fibrous Sheath-Interacting Protein 2 (FSIP2). This protein is a component of sperm’s fibrous sheath.

“The fibrous sheath covers the tails of sperm found in humans, mice and other species in which fertilization occurs within the animal’s body,” Dr. Li explains in a media release. “It offers the sperm tails flexibility and strength, which is necessary for sperm to swim in the dense and sticky medium of the human body before they meet the egg. Interestingly, animals whose sperm swim through water because fertilization occurs outside of the body, such as fish, either do not have the FSIP2 protein or, at most, a defective version.”

To study this particular mutation and the function of FSIP2, researchers examined two groups of mice. One group was engineered to have the same FSIP2 mutation as the one infertile man. The other group of mice was engineered to produce more than the normal amount of FSIP2 protein.

Results reveal mice with the mutation also became infertile, just like the human patient. Their semen contained fewer live sperm and more than half could not swim properly.

On the other hand, mice overproducing the FSIP2 protein remained fertile and actually had over seven times as many super-long sperm in comparison to normal mice. Super-long sperm are able to swim faster, making them more likely to fertilize an egg and reproduce.

What makes FSIP2 so important to sperm?

Researchers say sperm in the mice with the FSIP2 mutation had less of the protein which makes up the main components of sperm, including the sheath, the mitochondrial power generators, and the acrosomal vesicle. Those who produce more FSIP2 however, were able to create more sperm tail proteins.

Li, Sun, and their team believe the findings point to a potential treatment for poor sperm quality. This infertility cure may come either in a drug which restores sperm movement or by finding a way to correct this mutation.

The findings appear in the journal Development.

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