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.

Human T cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus-1 (HIV-1) are representative human retroviruses. To develop prophylactic vaccines and more effective medicines, small animal models for the virus infection are useful if they can be infected with the viruses. We constructed a transgenic (Tg) rat expressing human CRM1 (hCRM1), a cellular cofactor of Rex, and showed that T cells derived from Tg rats allowed production of HTLV-1 as efficiently as human T cells. However, viral load in Tg rats was not elevated so much. Our trials of various infection methods including oral administration to neonates failed to improve viral load, suggesting another barrier. During exploration we found lower rate of infection to rat dendritic cells (DC) than human DC, and administration of cyclosporine A (CSA) and As2O3 restored the infection rates. These results suggest the presence of inhibitor(s) that act during the entry process in rat DC.We also constructed Tg rats expressing human CD4, CCR5, CRM1, and CyclinT1, a cofactor of Tat to develop a model for HIV-1 infection. T cells and macrophages of the Tg rats supported production of infectious virus at levels approximately 10-40% of that detected in human cells. HIV-1 was efficiently infected to macrophages but not to CD4+ T cells. CSA and As2O3 restored the infection rates, suggesting the presence of inhibitor(s) that act during the entry process in rat CD4+ T cells.