Semen Fibers Shuttle RNA Into Sperm, Then Mouse Embryos, Study Finds

Tiny protein fibers in semen can help RNA from the surrounding fluid get inside sperm cells and, in laboratory experiments, on into mouse embryos, according to a study in the journal Molecular Cell, as reported by ScienceAlert. The fibers have an amyloid structure, a type of protein arrangement best known from Alzheimer's disease.

The work points to a previously unknown route by which RNA could travel from seminal fluid into an embryo. The experiments used lab-made fibers and added RNA, and the researchers have not yet shown that the natural process changes anything in an embryo.

How the fibers work

A team led by structural biologist Anthony Fitzpatrick and physiologist William Mallen at Columbia University's Zuckerman Institute studied the fibers. Sperm carry more than DNA. They also carry RNA molecules that can contribute to early embryonic development. Some RNA molecules hold instructions for making proteins, while others help regulate gene activity.

The researchers focused on a small fragment of an enzyme made by the prostate, called prostatic acid phosphatase. The fragment carries a positive electrical charge, and RNA carries a negative one. In the lab, the two bound together, formed tiny droplets and then developed into fibers containing RNA. The fragment alone stayed dissolved, so the RNA helped assemble its own carrier. Fitzpatrick told ScienceAlert that the cargo is helping build the vehicle that carries it.

These fibers differ from the ones in Alzheimer's disease. According to the report, they are built from a fragment of a semen protein, form outside cells in healthy men and can be taken apart again. In human seminal fluid, the team also found small RNA molecules in a fraction containing amyloid fibers. Many of the identifiable sequences were fragments of transfer RNA, which normally helps assemble proteins.

Watching fibers enter sperm

Finding RNA next to the fibers did not prove that the fibers get into sperm, because a fiber stuck to a cell's surface can look much like one inside it under some imaging conditions. To get around this, the team attached tiny gold particles to lab-made fibers. They used bull sperm for detailed imaging because the cells are relatively large. A technique that builds three-dimensional images of frozen cells showed labeled fibers inside the sperm.

More electron microscopy and live-cell imaging supported the result, and separate experiments showed that human and mouse sperm also took up the fibers. Fitzpatrick said that the sperm took the fibrils up whole and moved them along the tail, through the midpiece and into the head.

From sperm to embryo

In laboratory fertilization experiments with mouse sperm and eggs, the team exposed sperm to fibers made from human fragments before fertilization. Those fragments later turned up in two-cell mouse embryos. When the fibers were loaded with RNA carrying heavier forms of carbon and nitrogen, more labeled RNA reached the embryos than when fibers were absent.

The team also tested whether the delivered RNA could work. They used RNA with instructions for a protein that glows green, which shows the instructions were used. Embryos from sperm given the RNA with fibers contained at least ten times as much of the protein as embryos from sperm given the same RNA without fibers.

Separate tests showed that a protein called clusterin sped up the release of RNA from the fibers. Clusterin was also found in the embryos, but its role in releasing RNA there remains to be confirmed.

Why it matters: what the findings do and do not show

For now, this is basic biology. The findings describe a mechanism, not a treatment or a test. No human embryos or natural conceptions were studied, and estimates of how much the sperm took up varied between measurement methods. Fitzpatrick said the team has not yet shown whether naturally occurring fibers carrying their usual RNA make a difference in an embryo.

Mallen said the longer-term interest lies in inherited conditions. He noted that recent papers have shown that metabolic disorders such as insulin resistance can pass down the paternal line in mice, and that RNA is thought to be the means. Learning how such epigenetic effects work, he said, could bring researchers closer to treating or preventing them. ScienceAlert also reported that understanding the route could help researchers design new tools for delivering RNA.

What remains unknown

What happens to the fibers after they reach an embryo is unclear. Fitzpatrick said the team does not know whether they are cleared, left in place or seed further aggregation. As Fitzpatrick put it, “This is wild biology,” but the open questions mean the result is an early step rather than a settled finding.

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Around Prague, based on reporting by ScienceAlert