A HYALURONIDASE ACTIVITY OF THE SPERM PLASMA-MEMBRANE PROTEIN PH-20 ENABLES SPERM TO PENETRATE THE CUMULUS CELL LAYER SURROUNDING THE EGG

A typical mammalian egg is surrounded by an outer layer of about 3,000 cumulus cells embedded in an extracellular matrix rich in hyaluronic acid. A current, widely proposed model is that the fertilizing sperm, while it is acrosome intact, passes through the cumulus cell layer and binds to the egg zona pellucida. This current model lacks a well-supp orted explanation for how sperm penetrate the cumulus layer. We report that the sperm protein PH-20 has a hyaluronidase activity and is pres ent on the plasma membrane of mouse and human sperm. Brief treatment w ith purified, recombinant PH-20 can release all the cumulus cells surr ounding mouse eggs. Acrosome intact mouse sperm incubated with anti-PH -20 antibodies can not pass through the cumulus layer and thus can not reach the zona pellucida. These results, indicating that PH-20 enable s acrosome intact sperm to penetrate the cumulus barrier, reveal a mec hanism for cumulus penetration, and thus provide the missing element i n the current model.