Immunohistochemical demonstration of cyclooxygenase-2 (COX-2) and prostaglandin receptors EP2 and FP expression in the bovine intercaruncular uterine wall around term

Abstract

During parturition, uterine-derived prostaglandins (PG) play an outstanding role regarding the functional elimination of the corpus luteum and the promotion of uterine contraction. The rate-limiting enzyme cyclooxygenase-2 (COX-2), highly regulated in a cell-type and localization specific manner throughout pregnancy, is involved in uterine prostanoid production. Prostaglandins exert their effects via G-protein-coupled receptors. Distribution and cellular localization of these receptors are decisive factors for prostaglandin-mediated actions. Since both COX-2 and PG receptors have only been assessed during pregnancy in the cow, these parameters were localized immunohistochemically near term to evaluate their specific role at parturition. Thus, during two periods, segments of the intercaruncular uterine wall were collected from cows at slaughter being eight and nine months pregnant, from cattle during caesarean section, and after spontaneous calving. Results reveal that COX-2 was mainly localized in the cytoplasm of surface epithelial cells with a high expression in animals with induced parturition. The enzyme could also be found in lower concentrations within the glandular epithelium without any effect of gestational time or labour. In contrast to relaxant prostaglandin E receptor type 2 (EP2), not showing any change in all tissue layers observed, contractile prostaglandin F(2alpha) receptor (FP) was modulated during the peripartal period revealing a peak expression in animals with induced parturition. FP was localized in surface and glandular epithelial cells as well as in endometrial stroma and myometrial smooth muscle cells. Our study indicates that labour and induction of parturition may have an effect on amounts of immunohistochemically detectable COX-2 and FP. EP2 remains rather unchanged during the peripartal period. COX-2 and FP thus contribute via changes in amount and distribution to mechanisms associated with parturition. During parturition uterine derived prostaglandins (PG) play an outstanding role 2 regarding the functional elimination of the corpus luteum and the promotion of uterine 3 contraction. The rate-limiting enzyme Cyclooxygenase-2 (COX-2), highly regulated in 4 a cell-type and localization specific manner throughout pregnancy, is involved in 5 uterine prostanoid production. Prostaglandins exert their effects via G protein-6 coupled receptors. Distribution and cellular localization of these receptors are 7 decisive factors for prostaglandin-mediated actions. Since both, COX-2 and PG 8 receptors have only been assessed during pregnancy in the cow, these parameters 9were localized immunohistochemically near term to evaluate their specific role at 10 parturition. Thus, during two periods, segments of the intercaruncular uterine wall 11 were collected from cows at slaughter being eight and nine months pregnant, from 12 cattle during caesarean section, and after spontaneous calving.

Investigations into the mechanisms controlling parturition in cattle

“…The substantial upregulation of PTGS2 in UTC supports the concept that these cells are the primary source of prostaglandins in prepartal cows including PGF 2a . This conclusion is substantiated by earlier observations that have shown that UTC also express aldoketoreductase 1B5 (AKR1B5), an enzyme with a significant PGF synthase activity (Madore et al 2003, Schuler et al 2006b) and that PTGS2 expression in the bovine uterus around the time of spontaneous prepartal luteolysis is only low in comparison with the expression in the cotyledons (Fuchs et al 1999, Wehbrink et al 2008. The contribution of the placenta to systemic maternal PGFM concentrations is further supported by observations in D272 cows, in which -albeit on a low levela decrease in maternal PGFM concentrations was observed after disruption of the fetoplacental circulation following the surgical removal of the fetus (Fig.…”

“…However, as previously assumed, the release of oxytocin and the trauma set to the endometrium during expulsion of the fetus may contribute to the upregulation of endometrial PTGS2 expression in the immediate postpartal period (Fuchs et al 1999, Wehbrink et al 2008. High postpartal PGFM levels have been previously described in cases of RFM after glucocorticoid-induced parturition, whereas in non-RFM animals a rapid decline occurred after fetal expulsion (Königsson et al 2001).…”

“…These observations may indicate that the extraplacental prostaglandin source may initially have been attenuated by the presence of suppressive factors provided by the intact fetoplacental circulation or the absence of additional stimulatory factors. There is strong evidence that the uterus is the source of this postpartum increase, as PTGS2 expression in the uterus of late pregnant cows is only low until the expulsion of the calf, after which a rapid and significant upregulation has been shown to occur specifically in the intercaruncular endometrium (Fuchs et al 1999, Wehbrink et al 2008. Our study suggests that withdrawal of progesterone is a key event B A Figure 4 Expression of (A) cyclooxygenase 2 (PTGS2) and (B) 17a-hydroxylase-C17,20-lyase (CYP17A1) in placentomes from cows at induced parturition on days 271-272 (group AG: aglepristone, group PG: cloprostenol, group GC: dexamethasone), from day 272 pregnant animals and from cows at spontaneous parturition (group NT).…”

Folate-targeted paclitaxel-conjugated polymeric micelles inhibits pulmonary metastatic hepatoma in experimental murine H22 metastasis models

“…After assessing different tissue areas or the cytoplasm within the pictures, the mean gray value per lung tissue was calculated, as reported. 34 As shown in Figure 5 and Table 1, the microscopic tumor metastasis colonies detected by HE decreased in the drug groups in the order of PTX , M(PTX) , FA-M(PTX) when the equivalent dose of PTX is 15 mg/kg or 30 mg/kg; furthermore, a dose-dependent therapeutic effect was indicated.…”

Antitumor activity of folate-targeted, paclitaxel-loaded polymeric micelles on a human esophageal EC9706 cancer cell line

“…After assessing different tissue areas or cytoplasm within the pictures, a mean gray value per tumor tissue was calculated for further statistical analysis, as reported elsewhere. 35 The nuclei of the esophageal cancer cells were stained blue by hematoxylin, and the brown granules in the cytoplasm demonstrated apoptosis of cells, as shown in Figure 7A. Statistical analysis of the gray value from the TUNEL assay was performed in Figure 7B, which revealed differences between the drug groups and the control group (P , 0.01) on day 12 after intravenous administration.…”