CONICET | Buscador de Institutos y Recursos Humanos

SPHINGOSINE 1-PHOSPHATE TRIGGERS ACROSOME EXOCYTOSIS IN HUMAN SPERMATOZOA TROUGH A MEMBRANE RECEPTOR Suhaiman Laila, Mayorga Luis S., Belmonte Silvia A. Laboratorio de Biología Celular y Molecular, IHEM- CONICET, Fac. Ccias Médicas, U.N. de Cuyo Mendoza The acrosome is an exocytic granule that overlies the spermatozoan nucleus. In response to progesterone or zona pellucida, it undergoes calcium-regulated exocytosis. To determine if lipid molecules may activate signaling pathways similar to those triggered by physiological acrosome reaction (AR) inducers, we tested the effect of sphingosine 1-phosphate (S1P). In other cell types different S1P receptors have been described. These receptors are members of the lysophospholipid receptor family and are associated with different G proteins. By using functional assays, we observed that S1P induces AR in intact sperm. Its effect was inhibited by BAPTA suggesting that it depends on the presence of extracellular calcium. This result is consistent with the hypothesis that S1P activates exocytosis by a receptor-mediated mechanism that opens SOC channels. To confirm this hypothesis, we used Ni2+, an inhibitor of SOC channels which blocked progesterone and also S1P triggered exocytosis. As expected, no effect of S1P was observed in permeabilized sperm, where opening of SOC channels is not stimulatory by itself because of the absence of calcium in the medium. Furthermore, voltage-dependent calcium channel inhibitors, such as verapamil and nifedipine, efficiently blocked S1P induced AR. This is the first evidence suggesting that S1PR are present in sperm cells. Keywords: sperm, acrosome reaction, calcium and Sphingosine 1-phosphate

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