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United States Department of Agriculture

Agricultural Research Service

Title: Inhibition of Vascular Endothelial Growth Factor Signaling Blocks Primordial Follicle Activation in Bovine Ovarian Cortical Cultures

Authors
item Cushman, Robert
item Allan, Mark
item Clopton, Debra - UNIV NEBRASKA, LINCOLN
item Echternkamp, Sherrill
item Cupp, Andrea - UNIV NEBRASKA, LINCOLN

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: April 24, 2006
Publication Date: July 1, 2006
Citation: Cushman, R.A., Allan, M.F., Clopton, D.T., Echternkamp, S.E., Cupp, A.S. 2006. Inhibition of vascular endothelial growth factor signaling blocks primordial follicle activation in bovine ovarian cortical cultures [abstract]. Biology of Reproduction. (Supplement):144. (Abstract #325)

Technical Abstract: Depletion of the ovarian reserve is associated with the end of reproductive life in mammals, and is associated with activation of primordial follicles for further development. Therefore, understanding the mechanisms regulating follicle activation could lead to methods to increase lifetime productivity of female domestic livestock and enhance reproductive outcomes in women. In previous studies, inhibition of Vascular Endothelial Growth Factor (VEGF) signaling through the VEGF receptor decreased primordial follicle activation in neonatal rat ovary cultures. Therefore, we hypothesized that inhibition of the VEGF receptor signal cascade would also inhibit primordial follicle activation in bovine ovarian cortical cultures. Ovaries were collected by mid-line laparotomy from neonatal calves (n = 5) at 44 +/ 1.2 days of age, and the ovarian cortex was dissected from the medulla. Ovarian cortical pieces (2 pieces/well) were cultured in serum-free medium, with 0, 2, 4 or 8 uM of VEGF receptor tyrosine kinase inhibitor (VEGF-TKI) or DMSO (vehicle control) for 10 days in duplicate wells. VEGF-TKI was replenished every day and medium was changed every other day. On Day 0 or Day 10, cortical pieces (4 pieces/calf/day/treatment) were collected and embedded in London Resin White resin for morphometric analysis. In control and DMSO-treated cultures, the number of primordial follicles per section decreased (Day 0 = 4.6 +/ 0.7 vs. Day 10 = 0.7 +/ 0.3; P < 0.001) and the number of primary follicles per section increased (Day 0 = 1.3 +/ 0.3 vs. Day 10 = 5.4 +/ 0.5; P < 0.001). Primordial follicle activation was not inhibited by 2 or 4 uM of VEGF-TKI; however, after 10 days in the presence of 8 uM VEGF-TKI, the number of primordial follicles per section was not different from Day 0 controls (3.4 +/ 0.4 follicles/section). Primordial follicles increased in diameter after 10 days in control and DMSO-treated cultures (Day 0 = 16.0 +/ 2.1 um vs. Day 10 = 26.0 +/ 2.1 um; P < 0.05), and 8 uM VEGF-TKI did not inhibit the growth of primordial follicles after 10 days (30.3 +/ 2.1 uM). Thus, VEGF-TKI (8 uM) inhibited primordial follicle activation in bovine ovarian cortical cultures. The current study supports previous results in the perinatal rat and indicates that VEGF may be a regulator of primordial follicle activation.

Last Modified: 12/26/2014
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