Effect of Prostaglandin F2α (PGF2α) Administration on the Luteotropic and Angiogenic Factors During Functional Luteolysis in the Bovine Corpus Luteum.

Abstract

The essential role of endometrium PGF2α in induction of the corpus luteum (CL) regression (luteolysis) is well documented in the cow. However, the following regulatory cascade of functional luteolysis is still not fully elucidated. The aim of the present study was therefore to determine the regulation patterns of local luteotropic factors (progesterone, oxytocin and insulin-like growth factor (IGF) family members) and angiogenic factors (vascular endothelial growth factor-A (VEGF) and angiopoietin (ANPT) family members) during functional luteolysis (first 12 h after PGF2α injection) in time-defined CL classes. Cows (n=4-5 per group) in the mid-luteal phase (days 8-12) were injected with the PGF2α-analogue (cloprostenol), and CLs were collected by transvaginal ovariectomy at 0 h, 0.5 h, 2 h, 4 h and 12 h after PGF2α injection. The mRNA expression was analyzed by a quantitative real-time PCR (Rotor-Gene 3000), and the protein concentration was evaluated by enzyme immunoassay (EIA) or radio immunoassay (RIA). Progesterone concentration in blood serum and in CL tissue as well as mRNA expression of progesterone receptor in CL tissue, were significantly downregulated at 12 h after PGF2α. Oxytocin and IGF-1 peptide concentrations rapidly declined after 0.5 h and remained at low level afterwards. The IGF binding protein (BP)-1 mRNA was strongly upregulated with the maximal level at 4 h after PGF2α. This may cause further reduction of bioactive free IGF-1 in tissue. The VEGF protein decreased also at 0.5 h, with a synchronous acute and temporal increase of angiopoietin (ANPT)-2 peptide concentrations (0.5 h and 2 h after PGF2α). The similar tendency of upregulation of ANPT-2 was found for mRNA expression level, whereas the level of ANPT-1 mRNA did not change. The results suggest that the acute decrease of the local luteotropic factors and of VEGF may play a key role during the early step of functional luteolysis. The increase of ANPT-2 after PGF2α suggests a change in vascular stability to enhance the cascade of functional luteolysis.