HYALURONIC ACID SYNTHESIS BY OVARIAN CUMULUS AND GRANULOSA CELLS

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The purpose of this project is to study the biological and biochemical processes involved in synthesizing and organizing the hyaluronic acid- rich extracellular matrix which surrounds most mammalian oocytes at the time of ovulation. This matrix is produced primarily by the about 1,000 cumulus which are initially closely adherent to the oocyte. In response to a gonadotropin surge these cells initiate hyaluronic acid synthesis and deposit it in the extracellular matrix. This process enlarges the cumulus cell-oocyte complex, and the fully expanded complex is ovulated about 10 hours later. We are studying this process with mouse cumulus cell-oocyte complexes in vitro. Three factors have been identified that are necessary fro expansion: (1) a soluble factor produced by the oocyte which induces hyaluronic acid synthesis, (2) FSH (or cAMP) which amplifies the synthetic response, and (3) a factor in serum required to retain the newly synthesized hyaluronic acid in the matrix. Topics of present interest include: (1) identifying the factor produced by the oocyte that is required to induce hyaluronic acid synthesis by the cumulus cells, (2) determining how the cumulus cells respond to this factor via second messenger systems, (3) identifying the about 40 kDa protein which is synthesized by the cells during the expansion process, (4) determining the role of this protein, which binds to the newly synthesized hyaluronic acid, in matrix formation, and (5) determining the role of the serum factor required to retain the newly synthesized hyaluronic acid in the matrix.