L26/O-040 Unraveling the egg coat architecture and how ZP2 cleavage ensures the polyspermy block

作者：L. Jovine · 发表于：Human Reproduction · 年份：2026 · DOI：10.1093/humrep/deag083.040

In addition to supporting the growth of the oocyte and protecting the developing embryo until it hatches, the mammalian egg coat or zona pellucida (ZP) carries out two major functions at fertilization. First, it mediates the initial interaction between gametes; then, it permanently blocks polyspermy after the first egg-sperm fusion event. Whereas there is significant variability in the molecules involved in the latter process, the basic egg coat architecture is highly conserved from mollusks to mammals, albeit with different requirements for gamete interaction in external and internal fertilizers. Our previous studies suggested how mollusk acrosomal protein lysin dissolves the egg coat non-enzymatically, following species-specific recognition of ZP-N domain repeats at the N-terminus of vitelline envelope receptor for lysin (VERL) – the primary sperm-binding subunit of the mollusk egg coat. Interestingly, ZP-N domain repeats also constitute the N-terminal region (NTR) of ZP2, a major glycoprotein subunit of mammalian ZP filaments. Post-fertilization cleavage of the ZP2 NTR is crucial for reproduction, as it creates an irreversible block to polyspermy, and ZP2 processing was proposed to regulate gamete interaction by inactivating a sperm-binding activity located upstream of the cleavage site. However, the specific molecular effects of ZP2 cleavage and their role in ZP hardening — a phenomenon that also takes place after fertilization — were not well understood. By combining X...