Dad’s Diet May Reach Embryos Via Alzheimer’s-Like Clumps In Semen

Lab Tests Show Sperm Absorb Alzheimer’s-Like Clumps That Carry RNA

Amyloid has a nasty reputation. It is the sticky protein buildup found in the brains of Alzheimer’s patients. Semen, it turns out, makes its own version, and lab experiments suggest it helps carry RNA, the molecule cells use to read genetic instructions, toward an embryo. That could be one way a father’s diet reaches his children.

A study in Molecular Cell found that semen contains naturally occurring amyloid fibrils, thread-like protein clumps that latch onto bits of RNA. In lab tests, sperm absorbed lab-made versions of them. In mouse fertilization experiments done in a lab dish, RNA riding on the fibrils showed up in early embryos, where a test RNA was turned into protein.

Researchers already knew that male mice fed high-fat diets carry altered RNA in their sperm, and that their pups show metabolic changes. How that RNA gets onto sperm has been a puzzle. The new work points to a possible route. It did not test diet, though, or any effect on offspring health.

Semen Proteins Grab RNA and Harden Into Amyloid Fibrils

Researchers from Columbia University and partner institutions focused on a fragment of a protein the prostate releases into semen. The fragment carries a strong positive charge, RNA carries a negative one, and the two cling together like magnets. Sperm meet these proteins during ejaculation, before their long trip toward an egg.

In a test tube, the pair gathered into liquid blobs, much like oil beading up in vinegar, even when human seminal fluid was added. Over about three days, those blobs hardened into amyloid fibrils. Adding RNA made the process far faster, and longer RNA strands sped it up more.

To confirm that semen makes these fibrils on its own, the team purified them from pooled semen bought from anonymous, healthy donors. The fibril material held the same prostate protein, plus small RNA fragments, the largest group being snippets of the RNA that helps cells build proteins.

Amyloid Fibrils Enter Sperm Cells From Cows, Mice, and Humans

Next came the question of whether sperm actually take the clumps in. Cow sperm, larger and easier to study, went first. The team attached tiny gold beads to lab-made fibrils so they would show up in 3D images of frozen sperm. Fibrils turned up in the midsection, the energy-making part, touching structures inside the cell. Only five of 74 prepared slices showed fibrils, and just two were clear enough to be certain, so the team added other methods.

Live video helped. Tagged fibrils crossed the outer membrane of cow sperm and settled inside within 45 minutes, and about 95% of the cow sperm tested contained them. Fibrils also built up inside mouse and human sperm, though no percentage was reported for those.

Human sperm were a tougher test. A different method, run on live human sperm, found only 2.44% took up fibrils, a number the researchers say may undercount because of conservative settings. When an enzyme stripped proteins off the sperm’s surface, that figure fell to 0.30%. That points to surface proteins as a possible way in, though none were identified.

Amyloid Fibrils Deliver RNA to Mouse Embryos in Lab Fertilization

Mouse sperm were exposed to human fibrils, then used to fertilize mouse eggs in a dish. Pieces of the human protein turned up in the sperm and in the resulting embryos, which were only two cells old. In a second round, glowing tagged fibrils were visible in about 20% of embryos.

Tracking RNA was the next test. With a traceable, lab-made RNA attached to the fibrils, embryos from fibril-exposed sperm held measurably more of it, based on three samples per group. A protein called clusterin, already present in semen, sperm, and embryos, loosened RNA from fibrils about twice as fast in test tubes, hinting at how the cargo gets released.

A final experiment used RNA carrying instructions for a glowing marker protein. Embryos from fibril-exposed sperm contained at least ten times more of that protein, measured with a technique that identifies molecules by weight. Some of the protein also appeared without fibrils, possibly from loose RNA slipping in on its own.

Amyloid Fibrils Hint at a Non-Viral Way to Deliver Genes

Gene therapies that use viruses as delivery trucks can trigger immune reactions. The authors say amyloid fibrils could, in theory, offer a virus-free option for delivering genetic material at fertilization, perhaps for families at high risk of passing on a genetic disorder. That is far from any clinic, and editing embryos would raise serious ethical questions of its own.

Every sperm and embryo experiment here used lab-made fibrils, and the RNA tests used RNA added from outside. Whether RNA found naturally in semen reaches embryos this way remains untested.

Amyloid’s bad reputation may be undeserved in at least one corner of the body. Whether these clumps also carry a father’s influence to his children is the question that will decide if the discovery matters.

---

Disclaimer: This article is informational only, not medical advice. It covers early laboratory research. Consult a health professional about personal health questions.

---