Abstract
BackgroundThe mechanisms regulating the function and regression of the corpus luteum (CL) have not yet been elucidated in detail. The regressed CL of cows was previously reported to be filled with unusual vessels like arteriovenous anastomosis (AVA); however how these vessels are being established during luteolysis remains unknown.MethodsThe bovine CL at different luteal stages and regressing bovine CL induced by prostaglandin F2α (PGF) were histologically analyzed using light and electron microscopic levels. The changes in mRNA expression of genes encoding α-smooth muscle actin (SMA; Acta2) and transforming growth factor β1 (Tgfb1) in luteal tissues were analyzed by quantitative RT-PCR.ResultsAVA-like vessels appeared in the regressed CL with a diameter less than 1.5 cm in which no functional luteal cells and macrophages were observed. Epithelioid cells in the AVA-like vessel wall were immunoreactive for SMA, and the lumen of the vessels were narrow. Immunoreaction for SMA was found in the tunica media of typical arteries and arterioles, and pericytes around capillary vessel. Cells with elongated cytoplasmic processes ―resident fibroblasts expressing vimentin― distributed in the CL parenchyma without any association with blood vessels are also immunoreactive for SMA, and accumulated around arteries and arterioles during the late-luteal stage. In the regressed CL, walls of arteries and arterioles consisted of more than two layers of epithelioid cells positive for both SMA and desmin, suggesting that they are myofibroblasts transformed from fibroblasts. The percentage of the area positive for SMA and the mRNA expression of Acta2 were significantly increased in the regressed CL; however, they did not alter when a luteolytic dose of PGF was injected in vivo and collected within 24 h after the injection. On the other hand, Tgfb1, a known regulator for myofibroblast transformation, was significantly increased in PGF-induced regressing CL as well as in the CL during the late-luteal stage.ConclusionsSMA-positive myofibroblasts accumulates around the arteries and arterioles to form AVA-like vessels during luteolysis in cows. PGF indirectly regulates myofibroblast transformation through enhancing the expression of TGFβ1. These peculiar AVA-like vessels may be involved in the regulation of blood flow in the bovine CL during luteolysis.
Highlights
The mechanisms regulating the function and regression of the corpus luteum (CL) have not yet been elucidated in detail
prostaglandin F2α (PGF) is a major luteolysin in cows, the molecular mechanisms by which PGF regulates functional and structural luteolysis currently remain unclear; its effects are known to be mediated by various intra-ovarian factors, such as endothelin 1, nitric oxide, angiotensin II, and interferon γ [5,6,7,8,9,10,11]
This study revealed the detailed morphology of AVAlike vessels appearing in the regressed bovine CL and how they are constructed during luteolysis
Summary
The mechanisms regulating the function and regression of the corpus luteum (CL) have not yet been elucidated in detail. Functional luteolysis is characterized by a decrease in serum progesterone concentrations and is followed by structural luteolysis, in which the volume of the CL decreases due to apoptotic death of luteal cells. Serum concentration of progesterone markedly decreases approximately 19 days after ovulation and this is accompanied by an increase in plasma PGF metabolites, which represents the production of PGF in the uterus [3]. PGF is a major luteolysin in cows, the molecular mechanisms by which PGF regulates functional and structural luteolysis currently remain unclear; its effects are known to be mediated by various intra-ovarian factors, such as endothelin 1, nitric oxide, angiotensin II, and interferon γ [5,6,7,8,9,10,11]
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