Harvey Florman, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Cell Biology
   Physiology

Other Affiliation(s):
   Biochemistry and Molecular Pharmacology
   Interdisciplinary Graduate Program

Mechanisms of Fertilization

Fertilization is the process by which sperm and egg fuse and the program of development is initiated.  This is controlled in mammals at two steps: 1) sperm first undergo “capacitation”, a physiological reprogramming that occurs within the female reproductive tract and that is essential for the expression of fertility; and 2) capacitated sperm interact with the egg.  Our work has focused on the molecular and cellular mechanisms that control these two events.  To this end, we apply a range of biophysical (single cell fluorescence imaging, patch clamp electrophysiology), biochemical and molecular techniques.

Studies of capacitation address the control of sperm signal transduction pathways that lead to fertility.  Ion fluxes are important regulators of this process and we have identified key roles of sperm membrane potential and pH.  In addition, we recently recognized a role of polycystic kidney disease proteins in capacitation.  Ongoing and future studies address the mechanisms by which factors from the female reproductive tract regulate these and other pathways, leading to sperm fertility.

 Sperm-egg interaction begins when sperm contact the egg extracellular matrix (the zona pellucida).  ZP3, a protein component of the zona pellucida, activates sperm and triggers a secretory event known as the acrosome reaction.  This is an obligatory event in gamete interaction that must be completed if sperm are to fuse with eggs, and disruption of the zona pellucida-evoked acrosome reaction is linked to several types of male infertility.  We have worked on the signal transduction cascade that is regulated by ZP3.  Specifically, we have focused on the intersecting roles of Ca²⁺ and Ca²⁺ channels, of phosphatidylinositol pathways, and protein kinases in the control of the acrosome reaction.

Selected Publications

Arnoult, C., Kazam, I.G., Visconti, P., Villaz, M., Kopf, G.S., and Florman, H.M.  (1999) Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation.  Proc. Natl. Acad. Sci. USA (USA) 96, 6757-6762.PMID: 10359785

O’Toole, C.M.B., Arnoult, C., Darszon, A., Steinhardt, R.H., and Florman, H.M.  (2000) Ca²⁺ entry through store-operated channels in mouse sperm is initiated by egg ZP3 and drives the acrosome reaction Mol. Biol. Cell 11, 1571-1584. PMID: 10793136 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14868

Jungnickel, M.K., Marrero, H., Birnbaumer, L., Lemos, J.R., and Florman, H.M.  (2001) Trp2 regulates the Ca²⁺ entry into mouse sperm triggered by egg ZP3.  Nature Cell Biology 3, 499-502. PMID: 12042831
http://www.nature.com/ncb/journal/v3/n5/pdf/ncb0501_499.pdf

Evans, J.P., and Florman, H.M. (2002)  The state of the union: the cell biology of fertilization.  Nature Medicine 8, S57-S63.

Jungnickel, M.K., Sutton, K.A., and Florman, H.M. (2003) In the beginning: lessons from fertilization in mice and worms.  Cell 114, 401-404. PMID: 12941269

Sutton, K.A., Jungnickel, M.K., Wang, Y., Cullen, K., Lambert, S., and Florman, H.M.   (2004) Enkurin is      a novel TRPC channel and calmodulin interacting protein from sperm. Dev. Biol. 274, 426-435. PMID: 15385169

Galantino-Homer, H.L., Florman, H.M., Storey, B.T., Dorinski, I., and Kopf, G.S. (2004)  Bovine sperm capacitation: assessment of phosphodiesterase activity and intracellular alkalinization on capacitation-associated protein tyrosine phosphorylation.  Mol. Reprod. Dev. 67, 487-500.  PMID: 14991741

Florman, H.M., and Ducibella, T. (2006)  Fertilization in mammals.  In: The Physiology of Reproduction, 3^rd Edition (J. Neill, ed.) Elsevier Press. San Diego: pp. 55-112.

Sutton, K.A., Jungnickel, M.K., Ward, C.J., Harris, P.C., and Florman, H.M. (2006) Functional characterization of PKDREJ, a male germ cell-restricted polycystin.  J. Cell. Physio. 209, 493-500.  PMID: 16883570
http://www3.interscience.wiley.com/cgi-bin/fulltext/112738197/PDFSTART

Jungnickel, M.K., Sutton, K.A., Wang, Y., and Florman, H.M. (2007) Phosphoinositide-dependent pathways in mouse sperm are regulated by egg ZP3 and drive the acrosome reaction.  Dev. Biol. 304, 116-126. PMID: 17258189
http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1892180&blobtype=pdf

Sutton, K.A., Jungnickel, M.K., and Florman, H.M. (2008) A polycystin-1 controls post-copulatory reproductive selection in mice. Proc. Natl. Acad. Sci. USA 105, 8661-8666. PMID: 18562295
http://www.pnas.org/cgi/content/full/105/25/8661

Potential Rotation/Thesis/Postdoctoral Projects

1. Sperm ion channels:  Patch clamping and ion imaging of sperm in order to study ion channel regulation.
2. Function of polycystic kidney disease proteins in sperm:  Structure/function analysis of sperm polycystins (PKD1-related and PKD2-related proteins), examining their role in sperm physiology, including capacitation.
3. Sperm-egg communication:  Signal transduction pathways in sperm that are activated by the egg and that lead to the control of sperm exocytosis.

Laboratory Personnel

Melissa K. Jungnickel- Instructor, Department of Cell Biology

Keith A. Sutton- Instructor, Department of Cell Biology

Academic Background

1972    B.A., Rutgers College
1982    Ph.D., University of Pennsylvania

Office: S7-304
Phone: 508-856-1675
Fax: 856-5612
E-mail: Harvey.Florman@umassmed.edu
Keywords: Signal Transduction, Male Reproductive Biology, Electrophysiology, Ion Channels, Imaging and Microscopy

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