RESOLVING THE LEDGER
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Add as preferred source Researchers at VIB, VUB and the Medical Research Council Laboratory of Molecular Biology (UK) have discovered a hidden feature of human sperm cells. Using advanced imaging technologies, they discovered specialized compartments within the sperm nucleus packed with proteasomes, which are responsible for breaking down and recycling proteins.
The findings, published in Nature Structural & Molecular Biology , offer an unprecedented look inside sperm cells and could open new avenues for understanding male fertility.
In human sperm cells, DNA is packed more tightly than almost anywhere else in nature. Yet the researchers found that the nucleus of these cells is not as densely filled as previously thought. Instead, it contains small DNA-free cavities that act as dedicated hubs for proteasomes, molecules that "recycle" proteins and help cells stay functional.
Using cryo-electron tomography , a technique that allows researchers to examine cells in their native state at extremely high resolution, the team showed that these cavities contain large numbers of proteasomes organized into distinct clusters. Interestingly, these cavities were first observed by microscopists many years ago, who named them "lacunae." However, what they contain and whether they play an important biological role have remained largely unknown.
"We were surprised to find that the human sperm nucleus contains so many of these specialized compartments and that they were filled with proteasomes," says Professor Tom Dendooven (VIB-VUB Center for Structural Biology). "It reveals an unexpected level of organization inside the sperm head and suggests these structures have an important biological role."
The team not only mapped where these protein-recycling molecules are located but also determined their structure in remarkable detail. This revealed unique features that distinguish sperm proteasomes from those found elsewhere in the body. Among the discoveries was a previously unknown variant of a sperm-specific proteasome component.
To understand when these structures appear, the scientists examined tissue from human testes. They found that the proteasome-rich compartments emerge during the final stages of sperm development, when the genetic material inside the cell is being dramatically reorganized and compacted.
This timing suggests that the proteasomes may help orchestrate key steps in the maturation of sperm cells. Because defects in this process can affect fertility, the findings provide an important foundation for future research into male reproductive health. These proteasomes could remain active after the sperm enters the egg and may help remodel the paternal genome during the earliest stages of embryonic development.
"These findings give us a new framework for studying how sperm cells develop and what happens immediately after fertilization," says Dendooven. "There is still much to learn, but we can now start exploring these processes with an unprecedented level of detail."
The study provides new insight into the biology of sperm cells and establishes a foundation for future work on fertility, reproductive health and early embryonic development.
Piotr Kolata et al, Molecular architecture and spatial organization of proteasomes in the human sperm nucleus, Nature Structural & Molecular Biology (2026). DOI: 10.1038/s41594-026-01870-z
Journal information: Nature Structural & Molecular Biology
Provided by VIB (the Flanders Institute for Biotechnology)
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