Rafael Fissore

My laboratory is interested in understanding the mechanism by which the sperm is able to induce activation and trigger development in mammalian eggs. It is widely known that at fertilization the sperm induces Ca²⁺ oscillations and this Ca²⁺ release is the signal responsible for triggering the majority of events that culminate in embryonic development. However, how the sperm first signals Ca²⁺release and oscillations in eggs remains to be elucidated. Therefore, a main topic of research in our laboratory is to identify the pathway and characterize the molecule(s) responsible for this specific event of Ca²⁺ signaling. We are using several techniques to approach this question including intracellular Ca²⁺ signaling, in vitro fertilization, intracytoplasmic sperm injection (ICSI), and the application of multiple agonists/antagonists of common signal transduction pathways. Phospholipase C zeta1 has emerged as the molecule most likely to represent the Ca²⁺-active component in sperm and we are presently pursuing the characterization of several important aspects of this molecule, including its association with fertility. We found that human patients whose sperm lack PLCzeta1 are sterile and this sterility is associated with inability to initiate Ca²⁺ responses. Another area of research in the laboratory involves the characterization of the functional maturation of IP3R1 in mouse oocytes and eggs. IP3R1 is the main channel that mediates Ca²⁺ release in oocytes and eggs. We have found that phosphorylation of these receptor affects its ability to mediate Ca²⁺ release.