The fibres are built from a fragment of the enzyme prostatic acid phosphatase (PAP), a protein produced by the prostate. When mixed in the laboratory, PAP fragments and RNA, carrying opposite electrical charges, bound together and formed droplets that developed into amyloid fibres containing RNA. "The cargo is helping build the vehicle that carries it," structural biologist Anthony Fitzpatrick told ScienceAlert.
Amyloids are best known for their association with Alzheimer's and other neurodegenerative diseases, but they also have functional roles elsewhere in the body. The fibres in semen form outside cells in healthy men and are assembled from a protein fragment different from the proteins that accumulate in Alzheimer's; they can be taken apart again. In human seminal fluid, the researchers also found small RNA molecules in a fraction containing the fibres; many identifiable sequences were fragments of transfer RNA.
Using cryo-electron tomography to generate 3D images of frozen sperm, the team found gold-labelled fibres inside bull sperm. Separate experiments showed that human and mouse sperm could also take up the fibres. The fibres were seen moving along the tail, through the midpiece and into the head. "Seeing those amyloid fibers inside sperm cells was just so extraordinary to me," said physiologist William Mallen.
In laboratory fertilisation experiments with mouse sperm and eggs, human PAP fragments from the fibres appeared in two-cell embryos. When the fibres carried RNA encoding a protein that emits green light, resulting embryos contained at least ten times as much of the protein as embryos from sperm given the same RNA without fibres, indicating that the RNA instructions had been used.
A protein called clusterin accelerated the release of RNA from the fibres in lab tests, though its role inside embryos is not yet confirmed.
No human embryos or natural conceptions were tested, and what becomes of the fibres after they reach an embryo remains unknown. "We do not know what becomes of them in the embryo, whether they are cleared, left in place, or seed further aggregation," Fitzpatrick said. He added that the team has not yet shown whether naturally occurring fibres with their usual RNA cargo alter anything in an embryo.
