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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Nutrition, Growth and Physiology » Research » Publications at this Location » Publication #339139
Title: Ovarian cortex from high A4 cows secretes excess A4, and exhibits increased oxidative stress, macrophage markers and arrested follicle development which can be partially rescued by angiogenic VEGFA Is

Author
item ABEDAL-MAJED, MOHAMED - University Of Nebraska
item HART, MARIAH - University Of Nebraska
item LARGEN, VALERIE - University Of Nebraska
item MAGAMAGE, MANJULA - Sabaragamuwa University Of Sri Lanka
item KURZ, SCOTT - University Of Nebraska
item SARGENT, KEVIN - University Of Nebraska
item BERGMAN, JEFFREY - University Of Nebraska
item MCFEE, RENEE - University Of Nebraska
item Cushman, Robert - Bob
item DAVIS, JOHN - Nebraska Medical Center
item WOOD, JENNIFER - University Of Nebraska
item CUPP, ANDREA - University Of Nebraska

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/11/2017
Publication Date: 7/10/2017
Citation: 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. 2017. Ovarian cortex from high A4 cows secretes excess A4, and exhibits increased oxidative stress, macrophage markers and arrested follicle development which can be partially rescued by angiogenic VEGFA Is [abstract]. Society for the Study of Reproduction Annual Meeting. Abstract #P385 (Scientific Program p. 251). Available: http://www.ssr.org/sites/ssr.org/files/uploads/attachments/node/482/ssr2017abstracts.pdf

Interpretive Summary:

Technical Abstract: We have identified a population of cows within the UNL physiology herd with excess androstenedione (A4) in follicular fluid and 17% reduction in calving rate. Because excess androgens can cause follicle arrest we hypothesized that 1) folliculogenesis would be disrupted in High A4 cows; and 2) vascular endothelial growth factor (VEGFA) isoform treatments could rescue disrupted folliculogenesis. Ovarian cortical pieces were collected from High A4 (n = 9) and Low A4 (n = 11) cows at ovariectomy with cultured pieces treated with 1) PBS; 2) VEGFA165 (50 ng/ml); 3) VEGFA165b (50 ng/ml); 4) VEGFA165+VEGFA165b (50 ng/ml each). After 7 days of culture, the cortical pieces were obtained for histology. Sections from each treatment group were stained with hematoxylin and eosin and follicular stages were determined by three different technicians. At collection, ovarian cortex from High A4 cows had more primordial follicles P = 0.001) while Low A4 cows had more primary (P = 0.01), secondary (P = 0.02) and antral follicles (P = 0.04). After the culture in PBS, ovarian cortex from High A4 cows had more primordial follicles (P = 0.04), while Low A4 cows had more primary (P = 0.0003), secondary (P = 0.0001) and antral follicles (P = 0.007). Thus, primordial follicles did not activate in ovarian cortex cultures from High A4 cows. Treatment with VEGFA165 increased follicular progression in ovarian cortex from both High and Low A4 cows. In comparison to PBS-treated controls, VEGFA165 increased follicular progression in ovarian cortex from High A4 cows to a greater extent than Low A4 cows in the early primary (P = 0.05), primary (P = 0.0001), and secondary follicle (P = 0.0001) stages. Concentrations of A4 were measured in daily media changes. The ovarian cortex from High A4 cows secreted greater amounts of A4 (P = 0.01; 42 fold higher) in the culture media compared to Low A4 cows during the entire 7 day period. To determine if there was oxidative stress or migration of macrophages into the cortex due 4HNE (oxidative stress marker) and CD68 (macrophage marker) antibodies were used. Ovarian cortex from High A4 cows had increased positive staining for both 4HNE and CD68; suggesting there was more oxidative stress and macrophages present. Ovarian cortex from High A4 cows secrete greater concentrations of A4 that may elicit increased oxidative stress and macrophage activation resulting in arrested follicle development. Angiogenic VEGFA isoforms can partially rescue follicle development and may be used to aid females with follicle arrest due to excess A4. This research was funded through USDA grant 2013-67015-20965.