Rafael A. Fissore

Professor of Developmental Biology

Phone: 413-545-5548
Fax: 413-545-6326
Email: rfissore@vasci.umass.edu

Ph.D.: University of Massachusetts, 1993
Postdoctoral Training: Harvard Medical School
Honors: CFNR Research Award-2002

Ca²⁺ Release Mechanisms in Mammalian Eggs During Maturation and Fertilization

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 isolate 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), protein purification using column chromatography, and the application of multiple agonists/antagonists of common signal transduction pathways.

In another line of research, we are trying to understand the regulation of Ca²⁺ release through the inositol 1,4,5-triphosphate receptor (IP3R). This receptor is thought to mediate the totality of Ca²⁺ release during fertilization in mammals. Furthermore, it undergoes specific degradation as the first cell cycle progresses, and this degradation appears to be exclusively associated with IP3 production. We are investigating whether or not changes in the cell cycle affect the conductivity of the receptor, and the pathway by which the receptor is degraded in mammalian eggs. To address these questions we are using kinase assays, western blotting, microinjection and inhibitors of the proteasome, expression of IP3R mRNAs and mutations of the receptor. We have also recently identified a new inhibitor of the IPR3R-1, KN-93, and are in the process of characterizing its mechanism of action.

Injection of SF induces egg activation

Representative recent publications:

Gordo A.C., Rodrigues P., Kurokawa M., Jellerette T., Exley G., Warner C., and R.A. Fissore (2002). [Ca²⁺]i Oscillations Signal Apoptosis Rather than Activation in In vitro Aged Mouse Eggs. Biology of Reproduction 66, 1828-1837. Abstract

Gordo A.C., Kurokawa M., Wu H., and R.A. Fissore (2002). Modifications of the Ca²⁺ release mechanisms of mouse oocytes by fertilization and by sperm factor. Molecular Human Reproduction 8, 619-629. Abstract

Smyth J.T., Abbott A.L., Lee B., Sienaert I., Nadif Kasri N., De Smedt H., Ducibella T., Missiaen L., Parys J.B., and R.A. Fissore (2002). KN-93 inhibits the type 1 inositol trisphosphate receptor independently of Ca²⁺/calmodulin protein kinase II inhibition. J. Biol. Chem. In Press. Abstract

Fukami K., Nakao K., Inoue T., Kataoka Y., Korokawa M., Fissore R., Nakamura K., Katsuki M., Mikoshiba K., Yoshida N., adn T. Takenawa (2001) Requirement of phospholipase C delta 4 for the zonal pellucida-induced acrosome reaction. Science 292:920-3. Abstract

Wu H., Smyth J., Luzzi V., Fukami K., Takenawa T., Black S., Allbritton N.L., and R.A. Fissore (2001) Sperm factor induces [Ca²⁺]i oscillations by stimulating the phosphoinositide pathway. Biology of Reproduction 64:1338-49. Abstract

Lee S., Fissore R.A., and R. Nuccitelli (2001) Sperm factor initiates capacitance and conductance changes in mouse eggs that are more similar to fertilization than IP3- or Ca²⁺-induced changes. Developmental Biology 232:127-48. Abstract

Stricker S.A., Swann K., Jones K.T., and R.A. Fissore (2000). Injections of Porcine sperm extracts trigger fertilization-like Ca²⁺ oscillations in oocytes of a marine worm. Experimental Cell Research 257: 341-347. Abstract

Jellerette T., He C.L., Wu H., Parys J.B., and R.A. Fissore (2000). Down-regulation of the inositol 1,4,5,-trisphosphate receptor in mouse eggs following fertilization or parthenogenetic activation. Developmental Biology 223, 238-250. Abstract

Abbot A., Fissore R.A., and T. Ducibella (1999). Incompetence of preovulatory mouse oocytes to undergo cortical granule exocytosis following induction of [Ca²⁺]i oscillations. Developmental Biology 207:38-48. Abstract

Fissore R.A., Longo F.J., Anderson E., Parys J.B., and T. Ducibella (1999). Differential distribution of inositol trisphosphate receptor isoforms in mouse oocytes. Biology of Reproduction 60:49-57. Abstract

Wu H., He C.L., Jehn B., Black S., and R.A. Fissore (1998) Partial characterization of the calcium-releasing activity of porcine sperm cytosolic extracts. Developmental Biology 203:369-81. Abstract

Wu H., He C.L., and R.A. Fissore (1998) Injection of a sperm factor induces activation in mouse eggs. Molecular Reproduction & Development 49, 37-47. Abstract

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