August 12, 2019

Interpretive Summary: Hormonal regulation of VEGFA in granulosa and theca cells

Interpretive Summary:  Hormonal regulation of vascular endothelial growth factor A (VEGFA) gene expression in granulosa and theca cells of cattle

By: Jackie Walling

A recent study in the Journal of Animal Science investigated hormonal regulation of vascular endothelial Growth Factor A (VEGFA) in bovine granulosa cells (GC) and theca cells (TC). VEGFA assists in endothelial cell growth and blood vessel formation. Without VEGFA, fertility declines. Large GC follicles are found to carry more VEGFA proteins and mRNA abundance than smaller ones. It is hypothesized hormones regulate VEGFA expression with increased intrafollicular estradiol (E2) stimulating VEGFA gene expression. This study explored the correlation between hormones and VEGFA expression. 

Small (1-5mm) and large (8-20mm) follicles collected from the ovaries of beef heifers were aspirated to study GC and TC. Follicle size, cell type, and the effects and interactions of different hormones and growth factors were analyzed in seven various experiments. Experiment 1 determined how VEGFA mRNA in GC and TC change during follicle growth. Experiment 2 and 3 focused on VEGFA mRNA abundance in SM-follicle GC. Experiment 2 looked at effects on known ovarian trophic factors, while Experiment 3 tested the effects of steroids and intraovarian factors regulating cell proliferation. Experiments 4 and 5 looked at the same factors in LG-follicles GC. Experiments 6 and 7 focused on similar factors in TC cells.

Results of the experiments are as follows. The overall abundance of VEGFA mRNA was greater in GC than TC. In TC alone, abundance was greater in SM-follicles. In SM-follicle GC, ovarian trophic factors decreased VEGFA mRNA. Most steroids and intraovarian factors had no effect on abundance except for E2F inhibitor, which increased abundance. In LG-follicle GC, ovarian trophic factors had no effect except for progesterone, which increased abundance. In LG-follicle TC, abundance was increased by E2F inhibitor, bone morphogenetic protein 4, fibroblast growth factor 9, LH (by itself), and epidermal growth factor (by itself).

From the results, VEGFA gene expression is greater in GC than TC. With TC, expression changes with the follicle size. It was found that manipulation of E2F transcription factors induce gene expression and abundance is controlled by autocrine, paracrine, and endocrine regulators. SM-follicle GC was more responsive to inhibitory effects likely because of less differentiation than LG-follicle GC. Several factors investigated in this study conflicted with previous results, which could be a result of different culture conditions. The study suggests VEGFA production is hormonally regulated and changes with cell size and differentiation. At this time, more research is needed to understand the extent of the effect hormones, ovarian trophic factors, and steroids have on VEGFA production.

To read the full article, visit the Journal of Animal Science.