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Ethics
Autumn 2016

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reproduction

human oocyte
In the human egg, Balbiani bodies (BB) hold organelles together in a spot next to the nucleus (n).
 

Researchers don’t yet know how immature egg cells, or oocytes, survive and protect their contents while they lie dormant for years in a woman’s ovaries, awaiting hormonal signals that ready them for fertilization.

But clues, say cell biologist Elvan Boke and her colleagues at HMS, might lie in Balbiani bodies.

The Balbiani body is one of the more striking features of an oocyte, although it has been slow to reveal its secrets. Scientists know that it is a membraneless ball made up of mitochondria, other organelles, and proteins, and that it breaks apart when the oocyte begins maturing into an egg, releasing the organelles into the cytoplasm.

“How do they form and disperse?” asks Boke, who is a postdoctoral researcher and first author of the study. “How do they stay together without a membrane? What is their biological function?”

Boke, together with colleagues at HMS and the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, reported online in Cell on July 28 that in the oocytes of Xenopus frogs, long a model organism for fertility research, the contents of Balbiani bodies are bound together by a protein called Xvelo that clumps into a dense network of amyloid fibers.

“Amyloids have a scary reputation as the causative agents of neurodegenerative diseases, but we know relatively little about their possible normal functions,” says Timothy Mitchison, the Hasib Sabbagh Professor of Systems Biology at HMS and senior author of the study. “Xvelo provides one of the few emerging examples of a normal amyloid.”

Because Xvelo loses its amyloid-like configuration as the egg matures, the researchers think the frogs’ Balbiani bodies could hold clues for how to break up toxic amyloids seen in human diseases such as Alzheimer’s and ALS.

At a fundamental level, the  study is notable because the team “found that cells can use a protein to create a compartment from scratch,” says Boke. “This scale of cytoplasmic organization hadn’t been reported before.”

“We think the dormant oocyte packs away the majority of its organelle and RNA content when it’s not needed,” Boke adds. “It’s unpacked when the oocyte activates and it’s time to use them.”

If further research shows that Balbiani bodies are indeed critical for keeping eggs viable for long periods of time, it could have implications for human egg freezing and fertility treatments.

Although Xvelo isn’t well conserved in evolution, it does have counterparts—Bucky ball in zebrafish, Oskar in fruit flies—that are responsible for organizing Balbiani bodies or similar structures. Despite different genetic sequences, those proteins have something in common: a portion of their structure—a prion-like domain—that makes them likely to self-assemble.

The researchers found that Xvelo has such a domain, too. When they removed it by mutating the gene for Xvelo, the protein no longer aggregated.

“Pathological amyloids don’t go away,” says Boke, “but those in Balbiani bodies dissolve when the oocyte matures. This could be important for understanding how to make ‘bad’ amyloids disappear.” 

Image: Elvan Boke

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