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Protein tangles behind Alzheimer’s disease may be critical for human reproduction

Semen has something in common with the brains of Alzheimer’s sufferers: Both contain bundles of protein filaments called amyloid fibrils. But although amyloid accumulation appears to damage brain cells, these fibrils may be critical for reproduction. A new study suggests that semen fibrils immobilize subpar sperm, ensuring that only the fittest ones make it to the egg.

“I’m sure that from the very first time scientists described semen fibrils, they must have been speculating what their natural function was,” says Daniel Otzen, an expert in protein aggregates at Aarhus University in Denmark, who did not participate in the research. “This seems to be the smoking gun.”

Researchers discovered semen fibrils in 2007. At first, they seemed like mostly bad news. Scientists showed that the fibrils, found in the seminal fluid together with sperm cells and other components, can bind to HIV, helping it get inside cells. But the fibrils are found in most primates, notes Nadia Roan, a mucosal biologist at the University of California, San Francisco. “If fibrils didn’t serve some beneficial purpose, they would have been eliminated over evolutionary time.” Because the way HIV fuses to cells is reminiscent of the way a sperm fuses to the egg, she wondered whether the fibrils facilitated fertilization.

In the new study, Roan and colleagues created synthetic amyloid fibrils, and tested whether they promoted fusion between sperm and egg in lab dishes. They were quickly disappointed. In the presence of fibrils, spermatozoa were slower. “Their tails weren’t beating as fast,” Roan says. A look under the microscope showed that fibrils bind to sperm cells, immobilizing them.

So the researchers moved on to a new idea. Perhaps the fibrils could help women eliminate bad sperm. Following intercourse, a woman’s immune cells flood her reproductive tract to get rid of potentially harmful microorganisms, Roan says. To see whether semen fibrils might be facilitating this process, the researchers incubated healthy sperm with or without the synthetic fibrils, and then measured how many sperm were being eaten up by immune cells. In the presence of fibrils, up to five times more sperm cells were devoured than in the absence of fibrils. Fibrils also promoted the removal of sperm that had been damaged with ultracold temperatures. Immune cells ate up to 1.5 times more defective sperm cells when fibrils were present than when they weren’t, the team reports in eLife.

According to Roan, semen fibrils might have at least two beneficial effects in living animals. One would be to eliminate sperm hanging out for too long in the female reproductive tract, as this might trigger an unwanted immune response that would kill off all sperm cells. The other would be to remove defective cells, giving healthy sperm a better chance to reach the egg.

A strategy that helps ensure that “only the best and the brightest” reach the egg would make sense, Otzen says. “There's nothing more important, from an evolutionary perspective, than being able to have a strongly viable offspring.”

However, more research is needed to understand how fibrils entrap sperm, Otzen says. Also, it remains to be seen whether the effects observed in a laboratory dish hold true in living animals. Still, he says, this novel quality control function of semen fibrils shows how “nature is much more complex and quirky than we think.”