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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Livestock Bio-Systems » Research » Publications at this Location » Publication #350801
Research Project: Improving Livestock Production by Developing Reproductive and Precision Management Technologies

Location: Livestock Bio-Systems

Title: Ovarian cortex from high A4 cows secrete excess steroid hormones contributing to arrested follicle development, increased oxidative stress and fibrosis which can be rescued by angiogenic VEGFA165

Author
item SPRINGMAN, S - University Of Nebraska
item ABEDAL-MAJED, M - University Of Nebraska
item HART, M - University Of Nebraska
item LARGEN, V - University Of Nebraska
item MAGAMAGE, M - University Of Nebraska
item KURZ, S - University Of Nebraska
item SARGENT, K - University Of Nebraska
item BERGMAN, J - University Of Nebraska
item MCFEE, R - University Of Nebraska
item Cushman, Robert - Bob
item DAVIS, J - Nebraska Medical Center
item WOOD, J - University Of Nebraska
item CUPP, A - University Of Nebraska

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2018
Publication Date: 7/2/2018
Citation: Springman, S.A., Abedal-Majed, M.A., Hart, M.L., Largen, V., Magamage, M.P., Kurz, S.G., Sargent, K.M., Bergman, J., McFee, R.M., Cushman, R.A., Davis, J.S., Wood, J.R., Cupp, A.S. 2018. Ovarian cortex from high A4 cows secrete excess steroid hormones contributing to arrested follicle development, increased oxidative stress and fibrosis which can be rescued by angiogenic VEGFA165 [abstract]. Society for the Study of Reproduction Annual Meeting. Abstract Program p. 308-309. Available: https://www.ssr.org/sites/ssr.org/files/2018_annual_meeting_abstracts_updated.pdf

Interpretive Summary:

Technical Abstract: We identified a population of cows within the UNL physiology herd with excess androstenedione (A4; High A4) in follicular fluid, are often anovulatory, 17% reduction in calving rate and 43-fold higher A4 secretion from ovarian cortex cultures. We also demonstrated that genetically un-related heifers at the U. S. Meat Animal Research Center (14 out of 17 tested) secreted 18-fold greater A4 into media from ovarian cortex cultures; suggesting, that the High A4 phenotype may be present in other herds. We hypothesized that ovarian folliculogenesis is disrupted in High A4 cows due to excess A4 synthesis by the ovarian microenvironment; and vascular endothelial growth factor A (VEGFA) isoform treatment would rescue folliculogenesis by decreasing A4 production. Ovarian cortical pieces were collected from High A4 (n = 5) and Control (n = 5) cows at ovariectomy and treated with PBS or VEGFA165 (50 ng/ml) for 7 days. Media was collected daily for steroid analysis. Ovarian cortex from High A4 cows and treated with PBS secreted greater (P = 0.004) concentrations of A4 but other steroids and steroid metabolites including 11-deoxycorticosterone, 11-deoxycortisol, 17-OHP, androsterone, DHEA-S, DHT, E2, P4, and testosterone compared to controls. Concentrations of A4 and other steroids and metabolites in blood plasma were not different in High A4 cows compared to controls. Treatment with VEGFA165 dramatically (P = 0.004) reduced the concentration of A4 and other steroid hormones secreted by the ovarian cortex of High A4 cows. Numbers of primordial follicles were greater (P = 0.004); however, there were fewer primary (P = 0.01), secondary (P = 0.0001) and antral follicles (P = 0.008) in uncultured High A4 cow ovarian cortex when compared to Control cows. Treatment with VEGFA165 for 7 days stimulated more follicular progression to the secondary (P = 0.0005) and antral (P = 0.02) stages in ovarian cortex from Control cows than High A4 cows. Further, ovarian cortex treated with PBS from High A4 cows had increased staining for markers of oxidative stress and fibrosis. Treatment with VEGFA165 reduced staining for oxidative stress and tended (P = 0.056) to reduce staining for fibrosis in High A4 ovarian cortex compared to controls. Taken together these results indicate that ovarian cortex from High A4 cows secrete greater concentrations of steroids hormones which may contribute to increased oxidative stress and fibrosis, leading to follicular arrest. VEGFA165 isoform treatment can rescue follicle development and reduce ovarian cortex steroid secretion. Thus, VEGFA165 may be a potential therapeutic to restore steroid ovarian microenvironment and enhance follicular maturation.