Immunohistochemical Localization of Cyclooxygenase-2 in Pregnant Rat Uterus by Sp-6 Acupuncture

2003 ◽  
Vol 31 (03) ◽  
pp. 481-488 ◽  
Author(s):  
Jeong-Sang Kim ◽  
Chang Su Na ◽  
Woo Jun Hwang ◽  
Byung Chul Lee ◽  
Ki Hyoung Shin ◽  
...  
Keyword(s):  
Acupuncture Treatment ◽  
Immunohistochemical Localization ◽  
Cyclooxygenase 2 ◽  
Uterine Contractility ◽  
Rat Uterus ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Complementary Method ◽  
Key Factor ◽  
Cox 2

As pregnancy advances, prostaglandins (PG) increase in the uterus, leading to elevated uterine contractility. Therefore, regulating the concentration of PG in the uterus can be a key factor for controlling the duration of labor. Since the synthesis of PGs in the uterus is catalyzed by cyclooxygenase-2 (COX-2), devising a tool to regulate the expression of COX-2 could provide a method for treating complicated labor. In this study, Sp-6 acupuncture treatment was evaluated for its potential in controlling uterine motility. Immunohistochemical methods showed the COX-2 enzyme was primarily found in the endometrium and myometrium of rat uterus. COX-2 expression in these two locations were intensified by pregnancy, but reduced by acupuncture at the Sp-6 acupoint. Uterine motility monitored during Sp-6 acupuncture was reduced by 28.15% (p < 0.05) and 19.88% (p < 0.05) in pregnant rats and non-pregnant rats, respectively. The significant reduction of uterine motility in pregnant rat suggests a role for Sp-6 acupuncture in regulating the expression of COX-2 during pregnancy. These results suggest that Sp-6 acupuncture could be used as a complementary method for controlling labor in human pregnancy.

scholarly journals Immunohistochemical localization of procollagen types I and III during placentation in pregnant rats by type-specific procollagen antibodies.

1994 ◽  
Vol 42 (11) ◽  
pp. 1453-1461 ◽  
Author(s):  
M Kitaoka ◽  
K Iyama ◽  
H Yoshioka ◽  
M Monda ◽  
G Usuku
Keyword(s):  
Cell Layer ◽  
Maternal Blood ◽  
Immunohistochemical Localization ◽  
Fetal Blood ◽  
Placental Development ◽  
Developmentally Regulated ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Blood Capillaries ◽  
Trophoblastic Cells

To examine the sequential localizations of procollagen Types I (Pro I) and III (Pro III) during chorioallantoic placental formation in pregnant rats, we prepared polyclonal anti-rat Pro I- and III-specific antibodies. Biochemical analysis of a fraction containing [14C]-glycine-incorporated collagen from pregnant rat uteri showed that collagen Types I and III were actively synthesized during placental development. We examined 8-, 9.5-, 13-, and 20-day gestation rat uteri immunohistochemically. At Days 8 and 9.5, in the basal decidua facing the fetal cytotrophoblastic giant cell layer and implantation site, the immunoreactivity for Pro I was higher than that for Pro III. On Day 13, the enlarged myometrium and cytotrophoblastic cell layer showed increased immunoreactivity for Pro III. Unexpectedly, polygonal trophoblastic cells invading and modifying the maternal central artery showed intense immunoreactivity for Pro III. On Day 20, the fetal mesenchyme, large fetal blood vessels, and subendothelial stroma, including fetal blood capillaries, were more immunoreactive to Pro III antibody than to Pro I antibody in the labyrinth. Pro I and III synthesis and processing appear to be developmentally regulated and may be related to control of the microenvironment for supporting the fetus, control of the maternal blood supply stabilizing the fetoplacental physiological functions, and parturition.

scholarly journals Progesterone Receptor Plays a Major Antiinflammatory Role in Human Myometrial Cells by Antagonism of Nuclear Factor-κB Activation of Cyclooxygenase 2 Expression

2006 ◽  
Vol 20 (11) ◽  
pp. 2724-2733 ◽  
Author(s):  
Daniel B. Hardy ◽  
Bethany A. Janowski ◽  
David R. Corey ◽  
Carole R. Mendelson
Keyword(s):  
Progesterone Receptor ◽  
Target Genes ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Cyclooxygenase 2 ◽  
Nuclear Factor ◽  
Uterine Contractility ◽  
T47d Cells ◽  
Myometrial Cells ◽  
Cox 2

Abstract Spontaneous labor in women and in other mammals is likely mediated by a concerted series of biochemical events that negatively impact the ability of the progesterone receptor (PR) to regulate target genes that maintain myometrial quiescence. In the present study, we tested the hypothesis that progesterone/PR inhibits uterine contractility by blocking nuclear factor κB (NF-κB) activation and induction of cyclooxygenase-2 (COX-2), a contractile gene that is up-regulated in labor. To uncover mechanisms for regulation of uterine COX-2, immortalized human fundal myometrial cells were treated with IL-1β ± progesterone. IL-1β alone caused a marked up-regulation of COX-2 mRNA, whereas treatment with progesterone suppressed this induction. This was also observed in human breast cancer (T47D) cells. In both cell lines, this inhibitory effect of progesterone was blocked by RU486. Using chromatin immunoprecipitation, we observed that IL-1β stimulated recruitment of NF-κB p65 to both proximal and distal NF-κB elements of the COX-2 promoter; these effects were diminished by coincubation with progesterone. The ability of progesterone to inhibit COX-2 expression in myometrial cells was associated with rapid induction of mRNA and protein levels of inhibitor of κBα, a protein that blocks NF-κB transactivation. Furthermore, small interfering RNA-mediated ablation of both PR-A and PR-B isoforms in T47D cells greatly enhanced NF-κB activation and COX-2 expression. These effects were observed in the absence of exogenous progesterone, suggesting a ligand-independent action of PR. Based on these findings, we propose that PR may inhibit NF-κB activation of COX-2 gene expression and uterine contractility via ligand-dependent and ligand-independent mechanisms.

scholarly journals Hyperlipidemia impairs uterine β-adrenergic signaling by reducing cAMP in late pregnant rats

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Sakshi Chauhan ◽  
Subhashree Parida ◽  
E Prakash ◽  
G Srinivasan ◽  
Vivek Srivastava ◽  
...  
Keyword(s):  
High Cholesterol Diet ◽  
High Fat ◽  
Rat Uterus ◽  
Pregnant Rats ◽  
Camp Content ◽  
Pregnant Rat ◽  
Adrenergic Signaling ◽  
Adrenoceptor Agonist ◽  
Gi Protein ◽  
Tension Experiments

The aim of the present study was to reveal the effect of hyperlipidemia on β2- and β3-adrenergic signaling in late pregnant rat uterus. Hyperlipidemia was induced in female Wistar rats by feeding a high-fat high-cholesterol diet for 8 weeks before and after mating upto the 21st day of gestation. The effect of hyperlipidemia on β-adrenergic signaling was studied with the help of tension experiments, real-time PCR and cAMP ELISA in 21-day pregnant rat uterus. In tension experiments, hyperlipidemia neither altered the spontaneous contractility nor the oxytocin-induced contractions. However, it decreased the −logEC50 values of β2-adrenoceptor agonist, salbutamol and β3-adrenoceptor agonist, BRL37344. It also decreased the efficacy of adenylyl cyclase activator, forskolin. Further, there was a significant decrease in salbutamol and BRL37344-stimulated cAMP content in uterine tissues. However, there was no alteration in mRNA expressions of β2-adrenoceptor (Adrb2), β3-adrenoceptor (Adrb3) and Gs protein (Gnas) though there was a significant increase in the mRNA expression of Gi protein (Gnai). In conclusion, reduced cAMP content after beta-adrenergic receptor stimulation, which correlates with an increase in Gnai mRNA, may explain the mechanism of the impairment of uterine β-adrenergic signaling in hyperlipidemic pregnant rats. The clinical implication of the present study may relate to reduced myometrial relaxant response to β-adrenergic agonists in high fat-induced uterine dysfunction.

scholarly journals Progesterone decreases the relaxing effect of the β3-adrenergic receptor agonist BRL 37344 in the pregnant rat myometrium

Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 383-390 ◽  
Author(s):  
Renáta Minorics ◽  
Róbert Gáspár ◽  
Adrienn Gál ◽  
Anna Klukovits ◽  
George Falkay
Keyword(s):  
Functional Activity ◽  
Contractile Activity ◽  
Relaxation Effect ◽  
Inhibitory Effect ◽  
Uterine Contractility ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
The Right ◽  
Brl 37344 ◽  
Relaxing Effect

Although the published results regarding the function of the β3-adrenergic receptors (β3-ARs) in the regulation of smooth muscle activity are very promising, the question of the mechanism of β3-ARs' action in the pregnant myometrium cannot be fully answered by human investigations. To assess whether it possesses an essential role in the regulation of uterine contractility in pregnant rats, as in humans, we performed functional, western blotting and molecular biology experiments on the late-pregnant rat myometrium. The influence of progesterone on the function of the β3-ARs was also investigated. We demonstrated the presence and the functional activity of the β3-ARs in the late-pregnant rat myometrium. The maximum dose-dependent uterus-relaxing effect of the selective β3-agonist BRL 37344 was recorded at the end of pregnancy in rats, similarly as in humans. The extent of its relaxing action was regarded as moderate. The expression of β3-AR protein and mRNA remained unchanged during the investigated period. The administration of progesterone had no effect on the β3-AR mRNA and protein expression or the maximum relaxation effect of BRL 37344, but shifted the dose–response curve to the right and decreased the synthesis of the second messenger, cAMP. It can be concluded that the β3-ARs play an additional role in the regulation of the contractile activity of the pregnant rat uterus. The inhibitory effect of progesterone on the functional activity of the β3-ARs may have important consequences in the case of human application if this effect is also demonstrated in pregnant human myometrial tissue.

Fluprostenol-induced softening of the cervix of the pregnant rat

1983 ◽  
Vol 97 (2) ◽  
pp. 283-290 ◽  
Author(s):  
L. M. Williams ◽  
M. Hollingsworth ◽  
M. Dukes ◽  
I. D. Morris
Keyword(s):  
Binding Capacity ◽  
Direct Action ◽  
Prostaglandin E ◽  
Uterine Contractility ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Uterine Contractions ◽  
Prostaglandin F

Fluprostenol, an analogue of prostaglandin F2α, administered s.c. to rats on day 18 of pregnancy increased cervical creep, or softness, by the following day. Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions. Fluprostenol produced falls in serum progesterone concentrations, increases in 20α-dihydroprogesterone concentrations, no changes in oestradiol or relaxin concentrations and a reduction in the ovarian human chorionic gonadotrophin binding capacity in vitro. Fluprostenol was less potent in inducing cervical softness when administered per vaginam, and a dose which produced softening in pregnant rats was ineffective in ovariectomized steroid-maintained pregnant or pro-oestrous rats. The findings suggest that cervical softening by fluprostenol does not result from a simple direct action on the cervix or by increasing uterine contractions, but rather by an indirect hormonal action mediated by the ovaries. The results with the lowest dose of fluprostenol indicate that cervical softening could be produced without a sustained fall in serum progesterone concentrations. Fluprostenol is much more potent at increasing cervical softness in the pregnant rat than prostaglandin F2α or prostaglandin E2. With fluprostenol the ratio of dose to induce uterine contractility relative to that to produce cervical softness was greater than with these natural prostaglandins, indicating the greater selectivity of fluprostenol in the pregnant rat.

scholarly journals Expression and Biological Activity of Parathyroid Hormone-Related Peptide in Pregnant Rat Uterine Artery: Any Role for 8-Iso-Prostaglandin F2α?

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 626-633 ◽  
Author(s):  
Ferhat Meziani ◽  
Angela Tesse ◽  
Sandra Welsch ◽  
Hélène Kremer ◽  
Mariette Barthelmebs ◽  
...  
Keyword(s):  
Uterine Artery ◽  
Prostaglandin F2α ◽  
Cyclooxygenase 2 ◽  
Pcr Analysis ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Uterine Arteries ◽  
Pthrp Expression ◽  
D 20 ◽  
Pthrp Receptor

PTHrP is produced in vessels and acts as a local modulator of tone. We recently reported that PTHrP(1–34) is able to induce vasorelaxation in rat uterine arteries, but in pregnancy, this response is blunted and becomes strictly endothelium dependent. The present study aimed to get insights into the mechanisms involved in these changes because the adaptation of uterine blood flow is essential for fetal development. On d 20 of gestation, RT-PCR analysis of uterine arteries showed that PTH/PTHrP receptor (PTH1R) mRNA expression was decreased, whereas that of PTHrP mRNA was increased. This was associated with a redistribution of the PTHrP/PTH1R system, with both PTH1R protein and PTHrP peptide becoming concentrated in the intimal layer of arteries from pregnant rats. On the other hand, the blunted vasorelaxation induced by PTHrP(1–34) in uterine arteries from pregnant rats was specifically restored by indomethacin and a specific cyclooxygenase-2 inhibitor, NS 398. This was associated with an increase in cyclooxygenase-2 expression and in 8-iso-prostaglandin F2α release when uterine arteries from pregnant rats were exposed to high levels of PTHrP(1–34). Most interestingly, 8-iso-prostaglandin F2α itself was able to increase PTHrP expression and reduce PTH1R expression in cultured rat aortic smooth muscle cells. These results suggest a local regulation of uterine artery functions by PTHrP during pregnancy resulting from PTH1R redistribution. Moreover, they shed light on a potential role of 8-iso-prostaglandin F2α.

Alpha-tocopherol succinate increases cyclooxygenase-2 activity: Tissue-specific action in pregnant rat uterus in vitro

Life Sciences ◽  
2018 ◽  
Vol 192 ◽  
pp. 199-204 ◽  
Author(s):  
Anna Kothencz ◽  
Judit Hajagos-Tóth ◽  
Adrienn Csányi ◽  
Róbert Gáspár
Keyword(s):  
Cyclooxygenase 2 ◽  
Alpha Tocopherol ◽  
Rat Uterus ◽  
Pregnant Rat ◽  
Tissue Specific

scholarly journals Differential expression and regulation of cylooxygenases, prostaglandin E synthases and prostacyclin synthase in rat uterus during the peri-implantation period

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 139-151 ◽  
Author(s):  
Jing Cong ◽  
Hong-Lu Diao ◽  
Yue-Chao Zhao ◽  
Hua Ni ◽  
Yun-Qin Yan ◽  
...  
Keyword(s):  
Implantation Site ◽  
Prostaglandin E ◽  
Luminal Epithelium ◽  
Prostaglandin I2 ◽  
Rat Uterus ◽  
Pregnant Rats ◽  
Cox 2 ◽  
Prostacyclin Synthase ◽  
Implantation Period ◽  
Cox 1

It has been shown that both prostaglandin I2 (PGI2) and PGE2 are essential for mouse implantation, whereas only PGE2 is required for hamster implantation. To date, the expression and regulation of cyclooxygenase (COX) and prostaglandin E synthase (PGES), which are responsible for PGE2 production, have not been reported in the rat. The aim of this study was to examine the expression pattern and regulation of COX-1, COX-2, membrane-associated PGES-1 (mPGES-1), mPGES-2 and cytosolic PGES (cPGES) in rat uterus during early pregnancy and pseudopregnancy, and under delayed implantation. At implantation site on day 6 of pregnancy, COX-1 immunostaining was highly visible in the luminal epithelium, and COX-2 immunostaining was clearly observed in the subluminal stroma. Both mPGES-1 mRNA and protein were only observed in the subluminal stroma surrounding the implanting blastocyst at the implantation site on day 6 of pregancy , but were not seen in the inter-implantation site on day 6 of pregnancy and on day 6 of pseudopregnancy. Our data suggest that the presence of an active blastocyst is required for mPGES-1 expression at the implantation site. When pregnant rats on day 5 were treated with nimesulide for 24 h, mPGES-1 protein expression was completely inhibited. cPGES immunostaining was clearly observed in the luminal epithelium and subluminal stromal cells immediately surrounding the implanting blastocyst on day 6 of pregnancy. mPGES-2 immunostaining was clearly seen in the luminal epithelium at the implantation site. Additionally, immunostaining for prostaglandin I synthase (PGIS) was also strongly detected at the implantation site. In conclusion, our results indicate that PGE2 and PGI2 should have a very important role in rat implantation.

Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension

2007 ◽  
Vol 292 (5) ◽  
pp. R1943-R1955 ◽  
Author(s):  
Mariana Baserga ◽  
Merica A. Hale ◽  
Zheng Ming Wang ◽  
Xing Yu ◽  
Christopher W. Callaway ◽  
...  
Keyword(s):  
Animal Studies ◽  
Cyclooxygenase 2 ◽  
Adult Onset ◽  
Nephron Number ◽  
Pregnant Rat ◽  
Protein Levels ◽  
Increased Risk ◽  
Key Enzyme ◽  
Blood Pressures ◽  
Cox 2

Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11β-HSD2, and GR mRNA and protein levels, but upregulated expression of MR at birth. At day 21 of life, 11β-HSD2, GR, and also MR mRNA and protein levels were downregulated. UPI did not affect blood pressures (BP) at day 21 of life but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension.

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