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September 4th, 2025
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Guangzhou Women and Children\'s Medical Center, Guangzhou Medical University
developmental biology
bioRxiv

Separately prestored proteasome components to prevent polyspermy

Li, W.Open in Google Scholar•Wang, L.Open in Google Scholar•Liu, C.Open in Google Scholar•Wang, X.Open in Google Scholar•Guo, Y.Open in Google Scholar•Zhou, Q.Open in Google Scholar•Chen, Y.Open in Google Scholar•Wei, H.Open in Google Scholar•Huang, X.Open in Google Scholar•Liu, S.Open in Google Scholaret al.

To ensure genome stability across generations, an egg must be fertilized by only a single sperm. However, how sperm actively contribute to preventing polyspermy has remained unknown. Here, we demonstrate that testis-specific 20S proteasome core particles (CPs) are pre-stored within the sperm heads of both mice and humans. Upon fertilization, these testis-specific 20S CPs assemble with oocyte-derived 19S regulatory particles (RPs), forming chimeric proteasomes that efficiently degrade Fetuin B, which is ubiquitinated by the E3 ligase MARCH3. The clearance of Fetuin B triggers ZP2 cleavage and subsequent zona pellucida hardening, thereby blocking additional sperm entry. The newly assembled chimeric proteasome in the zygote represents a novel strategy to prevent polyspermy during fertilization in mammals.

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