Marie-France Pfenninger Assistant Professor Medicine / Cell and Developmental Biology Ph.D., University of Marseilles, 1972 Campus Box B158 School of Medicine, Room 0626 S/M Gastroenterology - Gastroenterology Phone: 303-315-7871, Fax: 303-315-5711 MF.Pfenninger@uchsc.edu

Research Interests:

The acrosome is a cap-like vesicular organelle located in the anterior two-thirds of the sperm head. The content of the acrosome is released by exocytosis during the acrosomal reaction, as the spermatozoon begins to penetrate the egg investments. The acrosomal content, composed of hydrolytic enzymes associated with a matrix, plays a key role in fertilization. The acrosome must be released before a spermatozoon can fertilize an oocyte. Spermatozoa devoid of the acrosome or with the acrosome intact are unfertile, as are sperm with low levels of hydrolytic enzymes.

The research goals of the laboratory are: 1) to study the synthesis and packaging of some of the content proteins of the sperm acrosome, with particular emphasis on the mechanisms by which these proteins are routed selectively to the developing acrosome during spermiogenesis and 2) to determine the function of some of these proteins in fertilization.

Work in the laboratory has been focused on studying some of the content proteins of the acrosome for which we have antibodies, proacrosin, acrogranin, auto antigen A1 (AA1), matrix proteins AM 50 and AM67. We showed that in the developing acrosome of spermatids these proteins, with the exception of AA1, are present in large complexes. The laboratory has determined the composition of some of these complexes and is in the process of studying their role in the biogenesis of the acrosome. We also have studied the maturation of the acrosome during sperm passage through the epididymis. We have observed that some of the acrosomal proteins get modified during epididymal transit. In particular, acrogranin gets proteolytically cleaved. This cleavage reveals an enzymatic activity, absent in the intact molecule. Experiments are in progress to determine the role of this enzyme in fertilization. The laboratory also is in the process of isolating the protease responsible for the cleavage and activation of acrogranin. Data from these studies are of fundamental interest for our knowledge of the intracellular routing and packaging of secreted proteins, and they should be important for our understanding of male infertility as well as for the design of new contraceptive agents.

Selected Publications

Maylie-Pfenninger MF. Developmentally regulated oligosaccharides in mouse spermatogenic cells. Arch Biochem Biophys. 1994 Jun;311(2):469-79.

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