VEGFA165 can rescue excess steroid secretion, inflammatory markers, and follicle arrest in the ovarian cortex of High A4 cows

A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A...

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Bibliographic Details
Published in:Biology of reproduction 2022-01, Vol.106 (1), p.118-131
Main Authors: Abedal-Majed, Mohamed A, Springman, Shelby A, Sutton, Courtney M, Snider, Alexandria P, Bell, Brooke E, Hart, Mariah, Kurz, Scott G, Bergman, Jeff, Summers, Adam F, McFee, Renee M, Davis, John S, Wood, Jennifer R, Cupp, Andrea S
Format: Article
Language:English
Subjects:
Androstenedione - analysis
Androstenedione - metabolism
Animals
Anovulation - drug therapy
Anovulation - physiopathology
Anovulation - veterinary
Anti-Mullerian Hormone - metabolism
Cattle
Cattle Diseases - drug therapy
Cytokines - metabolism
Female
Fibrosis
Follicular Fluid - chemistry
Inflammation - drug therapy
Ovarian Follicle - drug effects
Ovarian Follicle - physiopathology
Ovary - metabolism
Ovary - pathology
Oxidative Stress - drug effects
Protein Isoforms - administration & dosage
Tissue Culture Techniques - veterinary
Vascular Endothelial Growth Factor A - administration & dosage
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Summary:A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A4 cows and that vascular endothelial growth factor A would rescue the High A4 phenotype. In trial 1, prior to culture, High A4 ovarian cortex (n = 9) had greater numbers of early stage follicles (primordial) and fewer later-stage follicles compared to controls (n = 11). Culture for 7 days did not relieve this follicular arrest; instead, High A4 ovarian cortex had increased indicators of inflammation, anti-Mullerian hormone, and A4 secretion compared to controls. In trial 2, we tested if vascular endothelial growth factor A isoforms could rescue the High A4 phenotype. High A4 (n = 5) and control (n = 5) ovarian cortex was cultured with (1) PBS, (2) VEGFA165 (50 ng/mL), (3) VEGFA165B (50 ng/mL), or (4) VEGFA165 + VEGFA165B (50 ng/mL each) for 7 days. Follicular progression increased with VEGFA165 in High A4 cows with greater early primary, primary, and secondary follicles than controls. Similar to trial 1, High A4 ovarian cortex secreted greater concentrations of A4 and other steroids and had greater indicators of inflammation compared to controls. However, VEGFA165 rescued steroidogenesis, oxidative stress, and fibrosis. The VEGFA165 and VEGFA165b both reduced IL-13, INFα, and INFβ secretion in High A4 cows to control levels. Thus, VEGFA165 may be a potential therapeutic to restore the ovarian steroidogenic microenvironment and may promote folliculogenesis.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioab201