Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2alpha-induced regression in sheep.
Corpora lutea and blood samples were collected from superovulated ewes 0, 4, 8, 12 and 24 h after prostaglandin F(2alpha) (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 (Flt and KDR), basic fibroblast growth factor (FGF2) and receptor, angiopoietin (ANGPT) 1 and receptor Tie-2, endothelial nitric oxide synthase (NOS3), and angiotensin 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 for VEGF, Flt and KDR were positively correlated with changes in ANGPT2, Tie-2, and NOS3, 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.
Vonnahme
Kimberly A
KA
Department of Animal and Range Sciences, North Dakota State University, Fargo, 58105, USA.
Redmer
Dale A
DA
Borowczyk
Ewa
E
Bilski
Jerzy J
JJ
Luther
Justin S
JS
Johnson
Mary Lynn
ML
Reynolds
Lawrence P
LP
Grazul-Bilska
Anna T
AT
D000199:Actins / Q000032:analysis; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D003338:Corpus Luteum / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D003341:Luteolysis; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013480:Superovulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D000199:Actins; D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D015415:Biomarkers; D024042:Collagen Type I; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D011374:Progesterone; D015237:Dinoprost; D052250:Nitric Oxide Synthase Type III; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2