Expression pattern of HIF1alpha and vasohibins during follicle maturation and corpus luteum function in the bovine ovary

Abstract

The aim of this study was to characterize expression patterns of hypoxia-inducible factor-1alpha (HIF1A) and vasohibin family members (VASH1 and VASH2) during different stages of ovarian function in cow. Experiment 1: Antral follicle classification occurred by follicle size and estradiol-17beta (E2) concentration in the follicular fluid into 5 groups (<0.5, 0.5-5, 5-40, 40-180 and >180 E2 ng/ml). Experiment 2: Corpora lutea (CL) were assigned to the following stages: days 1-2, 3-4, 5-7, 8-12, 13-16 and >18 (after regression) of oestrous cycle and of pregnancy (months 1-2, 3-4, 6-7, >8). Experiment 3: Cows on days 8-12 were injected with a prostaglandin F2alpha (PGF) analogue and CL were collected before and 0.5, 2, 4, 12, 24, 48 and 64 hr after PGF injection. Expression of mRNA was measured by qPCR, steroid hormone concentration by EIA and localization by immunohistochemistry. HIF1A mRNA expression in our study increases significantly in follicles during final maturation. The highest HIF1A mRNA expression was detected during the early luteal phase, followed by a significant decrease afterwards. In contrast, the mRNA of vasohibins in small follicle was high, followed by a continuous and significant downregulation in preovulatory follicles. The obtained results show a remarkable inverse expression and localization pattern of HIF1A and vasohibins during different stages of ovarian function in cow. These results lead to the assumption that the examined factors are involved in the local mechanisms regulating angiogenesis and that the interactions between proangiogenic (HIF1A) and antiangiogenic (vasohibins) factors impact all stages of bovine ovary function.

Changes in the expression of prostaglandin family members in bovine corpus luteum during the estrous cycle and pregnancy

“…Moreover, in the ovary, prostaglandins regulate the expression of angiogenesis‐modulating factors in a luteal‐stage‐dependent manner (Atli et al, ; Weems et al, ; Zalman et al, ). In bovine CL, the mRNA and protein expression of the most important angiogenic family members (vascular endothelial growth factor [VEGF], fibroblast growth factor [FGF], insulin‐like growth factor, angiopoietin, and hypoxia‐inducible factor) were upregulated soon after the LH surge and remained elevated at least until the mid‐luteal phase (Berisha et al, ; Berisha, Schams, Rodler, Sinowatz, & Pfaffl, ; Jiang et al, ; Tesone, Stouffer, Borman, Hennebold, & Molskness, ). High expression and tissue levels of angiogenic factors during the early‐luteal stage (PTGF‐refractory days) suggest a survival function for both endothelial cells (EC) of the capillaries and steroidogenic cells of the CL (Berisha et al, ; Zalman et al, ).…”

Inflammation and angiogenesis in the corpus luteum

“…VEGF belongs to the heparin‐binding factor family and is the most remarkable regulator of angiogenesis in the CL . During inflammation, activated macrophages increase the production of VEGF by the cytokine TNFα, neutrophils themselves partially secreted VEGF and eosinophils have an indirect effect on the expression of VEGF via HIF . These findings indicate that the role of VEGF is essential in luteal inflammatory angiogenesis.…”

“…The physiological function of HIF1 is the regulation of angiogenesis, erythropoiesis and glycolysis . Recently, a cow CL study showed that the expression of HIF‐1 reached its highest level during the early luteal phase of the estrous cycle (period of angiogenesis), and then significantly decreased into the lower plateau during the mid and late luteal phases . In addition, the increased expression of HIF‐1 was detected during the early luteal phase in the monkey and in the human .…”

“…Recently, a study provided new insight that HIF1α demonstrated strong, positive expression in eosinophils in the early bovine CL. 62 It is widely accepted that HIF1α is a critical regulator of luteal angiogenesis via the upregulation VEGFA and FGF2 (discussed below). Furthermore, the concentration of VEGFA is significantly decreased when eosinophils are suppressed by dexamethasone in the early CL tissue of cattle.…”

“…However, there is lack of studies regarding the role of eosinophils in luteal angiogenesis. Recently, a study provided new insight that HIF1α demonstrated strong, positive expression in eosinophils in the early bovine CL . It is widely accepted that HIF1α is a critical regulator of luteal angiogenesis via the upregulation VEGFA and FGF2 (discussed below).…”