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Fellow: Dr. Wanzirai Muruvi
Mentor: Dr. Joanne Fortune
Contact Information: E-mail: jf11@cornell.edu - Phone: 607-253-3466
Sponsor: Lalor Foundation
Grant Number: N/A
Title: The Role of Kit Ligand in Activation of Bovine Primordial Follicles
Annual Direct Cost: $32,408
Project Period: 04/15/07-04/14/08
DESCRIPTION (provided by applicant): Very little is known about how activation of primordial follicles (i.e. initiation of growth) is regulated, especially in humans and domestic animals. Several growth factors stimulate follicle activation in newborn rodent ovaries in vitro, but the evidence for the role of kit ligand (KL) seems the most compelling. Our laboratory developed an in vitro model in which small pieces of bovine and baboon ovarian cortex are cultured with the medium supplement ITS+ (insulin, transferring, selenium + linoleic acid and BSA); wholesale "spontaneous" activation occurs, but few follicles develop beyond the primary stage. Recently, our laboratory found that activation does not occur when bovine cortical pieces are cultured in the absence of insulin (i.e., in TS+), suggesting that the insulin in ITS+ stimulates activation. Experiments conducted during the current fellowship showed that 1) KL increases the number of primary follicles in bovine cortical pieces cultured in TS+, but at a lower rate than with ITS+, and 2) ACK2, an antibody to the KL receptor, does not block activation in cortical pieces cultured with ITS+. We now propose to build on these exciting results by testing the hypothesis that activation stimulated by KL is more "normal" than activation with ITS+ and will, thus, promote the primary to secondary follicle transition (Specific Aim #1). In Specific Aim #2 we will compare the roles of KL and insulin further by determining if insulin stimulates the expression of mRNA for KL. These experiments will help identify mechanisms that regulate the initiation of follicle growth in cattle, an excellent model for human ovarian function, and may generate ideas that lead to the development of alternative methods to control female reproduction.
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