Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2α-induced regression in sheep
Corpora lutea and blood samples were collected from superovulated ewes 0, 4, 8, 12 and 24 h after prostaglandin F2α(PGF) analog injection on day 10 of the estrous cycle. Changes in vascular cell and fibroblast composition, apoptosis and mRNA expression for several angiogenic factors in the corpus luteum (CL) were determined. While peripheral progesterone concentration decreased at 24 h after PGF injection, CL weight did not change. The area of positive BS-1 lectin staining (endothelial cell marker), smooth muscle cell actin (SMCA; pericyte and SMC marker), collagen type 1 (fibroblast marker), and the rate of cell death changed in luteal tissues after PGF treatment. In association with these cellular changes, mRNA for several angiogenic factors including vascular endothelial growth factor (VEGF) and receptors (FltandKDR), basic fibroblast growth factor (FGF2) and receptor,angiopoietin (ANGPT) 1and receptorTie-2,endothelial nitric oxide synthase(NOS3), andangiotensin II receptor 1(AT1) were altered. Changes in endothelial cell marker expression were positively correlated with changes in VEGF and NO systems. In addition, changes in mRNA expression forVEGF,FltandKDRwere positively correlated with changes inANGPT2,Tie-2, andNOS3,indicating a functional relationship. This data demonstrates that after an initial increase, the endothelial component of the vascular bed decreases during PGF-induced luteal regression. However, SMCA expression remained high during luteal regression, potentially indicating a role of pericytes and vascular SMC in luteolysis, likely to regulate tissue remodeling and to maintain the integrity of larger blood vessels. Further, it appears that early regression may increase collagen type 1 production and/or expression by fibroblasts. Expression of angiogenic factors is influenced by PGF-induced luteolysis and may serve to maintain vascular structure in order to aid luteal regression.