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.
Additional current research in the lab is characterizing the Ca2+ channels that mediate Ca2 influx into oocytes and eggs during maturation and fertilization. Ca2+ influx is required both for acquisition of maturation competence and for embryo development. Our collaborative studies led to the discovery of a channel in mouse eggs, TRPV3, which mediates SrCl2 influx, a divalent cation commonly used for parthenogenetic activation. This channel however is not required for fertilization-mediated oscillations, and studies are focusing on characterizing these presently unknown channels.
Learn more at www.vasci.umass.edu/research-faculty/rafael-a-fissore
- PhD University of Massachusetts, 1993
- Postdoctoral Training: Harvard Medical School