Downregulation of Lymphatic Vessel Formation Factors in PGF_2α-induced Luteolysis in the Cow

Abstract

Prostaglandin F2α (PGF2α) induces luteolysis in cows and causes infiltration of immune cells, which resembles inflammatory immune response. Since the general immune response is mediated by the lymphatic system, we hypothesized that luteolysis is associated with generation of an immune response that involves lymphatic vessels in the bovine corpus luteum (CL). The CL was obtained from Holstein cows at the mid-luteal phase (days 10–12, ovulation = day 0) by ovariectomy at various time points after PGF2α injection. Lymphatic endothelial cell (LyEC) marker, endothelial hyaluronan receptor 1 (LYVE1), levels decreased significantly 12 h after PGF2α injection. Podoplanin, another LyEC marker, decreased from 15 min after PGF2α injection. PGF2α also diminished mRNA expression of lymphangiogenic factors, such as vascular endothelial growth factor (VEGF) C, VEGFD and VEGF receptor 3 (VEGFR3). During PGF2α-induced luteolysis, the levels of mRNA expression of tumor necrosis factor α (TNFα; the major pro-inflammatory cytokine) and chemokine (C-X-C motif) ligand 1 (neutrophil chemokine) were increased. On the other hand, chemokine (C-C motif) ligand 21, which regulates outflow of immune cells from tissues via the lymphatic vessels during an immune response, was decreased. This study demonstrated that the lymphatic network in the CL is disrupted during luteolysis and suggests that during luteolysis, immune cells can induce a local immune response in the CL without using the lymphatic vessels.

Repeated intrauterine infusions of lipopolysaccharide alter gene expression and lifespan of the bovine corpus luteum

“…There was no difference in the mRNA expression of TNFA between the LPS and the CON cycle. Following PGF 2α -induced luteolysis, TNFA increased significantly after 15 min but returned to initial values within 12 h (Nitta et al, 2013). It is possible that the reason we could not detect the increase in luteal TNFA was the variable time (relative to biopsy) of LPS-induced luteolysis.…”

Estradiol-17β Regulates Expression of Luteal DNA Methyltransferases and Genes Involved in the Porcine Corpus Luteum Function In Vivo

“…Elevated expression of PTGFR mRNA and protein has been observed in CLs on day 12 of pregnancy compared to day 12 of the estrous cycle [ 15 ]. A stimulating effect of PGF2α on luteal angiogenesis has been described in bovines [ 36 , 37 ]. Our previous studies revealed that E2 regulates the expression of the endometrial PTGFR gene and protein in the pig, and indicated the involvement of PGF2α-PTGFR signaling in angiogenic changes within the endometrium [ 11 , 12 , 38 ].…”