Amyloid fibers carry RNA into sperm and mouse embryos

Analysis of human seminal fluid found small RNAs in the fraction containing amyloid fibers. Many identifiable sequences were fragments of transfer RNA, molecules normally involved in assembling proteins.

Finding RNA beside fibers did not prove entry into sperm. A fiber attached to a cell surface can resemble one inside under some imaging conditions.

Researchers attached tiny gold particles to laboratory-made fibers so they could track them. They used bull sperm for detailed imaging because those cells are relatively large. Cryo-electron tomography, a method that builds three-dimensional images of frozen cells, showed labeled fibers inside bull sperm.

The study’s accompanying image shows amyloid fibrils in yellow inside a sperm cell. Additional electron microscopy and live-cell imaging supported the result. Separate experiments showed that human and mouse sperm could also take up the fibers.

Fitzpatrick reported that sperm took the fibrils in whole and moved them deep inside, along the tail, through the midpiece and up into the head. Mallen said: “Seeing those amyloid fibers inside sperm cells was just so extraordinary to me. There were hints of this happening earlier in our other experiments, but actually seeing this totally blew us away.”

From sperm to embryo

Before combining sperm with mouse eggs, the team exposed the sperm to fibers made from human PAP fragments. Human protein fragments appeared in the resulting two-cell mouse embryos.

To trace the cargo, the researchers used RNA containing heavier versions of carbon and nitrogen. Mass spectrometry, which distinguishes molecules by mass, tracked those labels. When the researchers included fibers, more labeled RNA reached the embryos.

They also loaded fibers with RNA instructions for a protein that emits green light. When sperm received RNA with fibers, the resulting embryos contained at least 10 times as much marker protein as embryos given the same RNA without fibers.

Separate tests showed that a protein called clusterin accelerated RNA release from the fibers. Clusterin also appeared in embryos, but the experiments did not confirm that it released RNA inside them.

What does this change for RNA delivery?

It gives researchers a testable carrier: oppositely charged RNA and amyloid-forming protein fragments can assemble into fibers, cells take them up, and cargo reaches fertilized eggs in this mouse system. The authors say understanding the route could help design RNA-delivery tools. That possibility remains experimental.

Mallen linked the mechanism to a broader question: whether RNA helps carry metabolic effects from fathers to embryos. He noted that recent work has shown insulin resistance can pass down the paternal line in mice and that scientists think RNA may be the mechanism.

Studying that epigenetic process—changes in gene activity rather than DNA sequence—could eventually aid treatment or prevention, he said. The present study did not test insulin resistance or any disease outcome.

The practical answer is that no clinical application is established. The work identifies a mechanism and a possible research tool. Nothing yet shows that naturally occurring fibers deliver enough functional RNA to change human embryo development.

The caveats matter

The embryo tests used mice, laboratory-made fibers and added RNA. Fitzpatrick said the team has not shown whether naturally occurring fibers, together with their normal RNA cargo, change anything in an embryo. Uptake estimates also varied between measurement methods.

Researchers do not know what happens to the fibers after they reach an embryo: they may be cleared, remain in place or seed further aggregation. The study demonstrates the route under test conditions, not its importance in natural reproduction.

The paper appeared in Molecular Cell under DOI 10.1016/j.molcel.2026.10.004.