VIB/VUB Team Reveals Hidden Sperm Proteasome Structures

Researchers at VIB (the Flanders Institute for Biotechnology), Vrije Universiteit Brussel (VUB) and the UK’s MRC Laboratory of Molecular Biology have discovered specialised proteasome-rich compartments hidden inside human sperm nuclei. Published in Nature Structural & Molecular Biology on 2 September 2026, the work uses cryo-electron tomography to map the structures and provides a new framework for studying sperm cell development, male fertility and early embryonic development.

In human sperm cells, DNA is packed more tightly than almost anywhere else in nature, yet the team found that the sperm nucleus is not as densely filled as previously thought. Small DNA-free cavities (historically named “lacunae” by microscopists but whose contents and role were largely unknown) act as dedicated hubs for proteasomes, the molecular machines that break down and recycle proteins. Using cryo-electron tomography, the researchers demonstrated that these cavities contain large numbers of proteasomes organised into distinct clusters, and identified a previously unknown variant of a sperm-specific proteasome component.

The team also examined human testis tissue and found the proteasome-rich compartments emerge during the final stages of sperm development, when the genetic material inside the cell is being dramatically reorganised and compacted. The timing suggests proteasomes may orchestrate key steps of sperm maturation, and could remain active after sperm enters the egg to help remodel the paternal genome during the earliest stages of embryonic development. Prof Tom Dendooven, VIB-VUB Center for Structural Biology, positioned the study as providing a new framework for studying sperm cell development and post-fertilisation events, with defects in this process potentially affecting fertility.

The commercial signal is a foundational discovery that could reshape male fertility diagnostics, reproductive medicine research and IVF assay development. Sperm-specific proteasome biology also offers a novel exploration angle for the growing protein degrader (PROTAC) drug discovery category. Expect Ferring Pharmaceuticals, Merck KGaA, Organon, Vitrolife and cryo-EM instrument suppliers Thermo Fisher and JEOL to sharpen their positioning as clinical translation progresses.

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