Inhibitory Effect of the Intrauterine Infusion of Phorbol 12-Myristate 13-Acetate and 1-Oleoyl-2-Acetylglycerol on the Decidual Cell Reaction in Rats1 (original) (raw)
Reproduction, 1983
Intrauterine instillation of oil, but not saline, induced both a decidual cell reaction and a marked elevation in the uterine PGF-\g=a\content of suitably sensitized ovariectomized mice. Uterine PGF-\g=a\concentrations were elevated within 5 min of the oil instillation, reached maximal levels within 30\p=n-\60min and then declined to near baseline levels again by 3 h. A similar increase in uterine PGF-\g=a\content in response to oil instillation was seen in non-sensitized females, although no decidual cell reaction developed. No significant changes in PGE or 6-oxo-PGF-1 content were observed. These results suggest that although the increase in uterine PGF-\g=a\ content is not solely due to the distension of the uterus after intrauterine injection, the increase is not necessarily sufficient to induce a decidual cell reaction.
Prostaglandin F2α and Its Receptor as Activators of Human Decidua
Seminars in Reproductive Medicine, 2007
Prostaglandins produced by the intrauterine tissues of both mother and fetus (myometrium, decidua, placenta, chorion, and amnion) are involved with all of the physiologies of parturition (membrane rupture, cervical dilatation, myometrial contractility, placental separation, and uterine involution). For parturition to occur, however, the intrauterine tissues need to first be activated to prepare for the work of labor, then stimulated to initiate labor. Prostaglandins normally are considered to be stimulators of the physiologies of labor. This review presents evidence that one prostaglandin, PGF 2a , and its receptor, FP, are also activators, especially of the decidua. Stimulated by cytokines, the decidual synthesis of PGF 2a and the expression of FP lead to increased matrix metalloproteinase activity, further enhancement of cytokine activity, increased decidual oxytocin and oxytocin receptor expression, decreased progesterone responsiveness, and possibly, enhanced expression of vascular endothelial growth factor. These collective actions prepare the decidua for its role in parturition.
Effect of deciduogenic stimuli on protein secretion by the mouse uterus
Reproduction, 1988
Instillation of oil into progesterone-primed, oestrogen-sensitized uteri of mice resulted in secretion patterns which were similar, but not identical, to those found on Day 5 of pregnancy. Stimulus-dependent responses common to pregnancy and the experimental decidual cell reaction included an early but transient increase in a 40 000 Mr basic protein and decreases in two other proteins. Some of the characteristic changes were also found after oil instillation in the progesterone-maintained 'non-receptive' uterus, even though subsequent decidualization did not occur. Instillation of cholera toxin, another deciduogenic substance, also resulted in patterns similar to those of pregnancy, including an increased secretion of a 25 000 Mr acidic protein which was only minimally produced during the oil-induced decidual cell reaction.
Metabolic factors regulating the generation of prostaglandins E1 and E2 by isolated rat uterus
Prostaglandins, Leukotrienes and Medicine, 1983
The generation and output of PEE2 and PGE, by isolated rat uterus incubated with or without glucose as well as the influence of different metabolic substrates and selective enzyme inhibitors on tissue formation and release of PGE material of the 1 and 2 series, were explored. The output of PEE2 was comparable with glucose, fructose, lactate or pyruvate as the substrate but diminished significantly in citrate-containing solution. In aub-&rate-free media uteri released more PGE than in the presence of glucose or other substrates. The PGEl z iberated was similar in glucose, fructose, lactate or pyruvate and decreased significantly in citrate or without substrate. 2-deoxy-D-glucose (2-DG), fluoride or arsenite failed to alter significantly the release of PEE2 whereas 2,4_dinitrophenol (ONP> evoked augmentation. The uterus released less PEEI after 2-DE or fluoride but not following the addition of DNP or arsenite. The results suggest that the synthesis and release of PGE2 and PGE, in the isolated rat uterus appear to be selectively modulated by different tissue metabolic pathways.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2008
Prostaglandin E(2) (PGE(2)) exerts diverse biological effects through four G-protein-coupled cell surface receptor subtypes, EP1-4. This study's objective was to characterize EP1-4 receptor mRNA expression within pregnant guinea pig myometrium during early implantation stage (gestation day [GD] 6) and late stage gestation (GD 50) and evaluate in vitro contractile activity of receptor subtype selective agonists. Using RT-PCR, qualitative gene expression patterns of EP2, EP3, and EP4 mRNA were detected in the myometrium and remained unchanged between the gestational ages. EP1 mRNA remained undetected in pregnant tissue. In vitro contractile activity was evaluated in GD 6 and GD 50 myometrium using vehicle and EP agonists PGE(2), 17-phenyl trinor PGE(2), sulprostone, misoprostol, and CP-533,536. All spasmogens in pregnant myometrium were EP1/EP3 selective agonists, though likely acting via EP3 receptors in this test model. CP-533,536--a highly selective EP2 receptor agonist--and the vehicle failed to induce myometrial contraction at both gestational ages.
The inhibitory effect of cytosolic fraction of human decidua on prostaglandin synthesis
Endocrinologia japonica, 1987
To elucidate the mechanism of suppression of prostaglandin (PG) production in decidua in early pregnancy, the PG synthetase activity of decidua and mid-secretory endometrium was studied. The microsomal fractions and their supernatants were prepared from the tissue by ultracentrifugation at 105,000 g. The standard incubation mixture consisted of the microsomal fraction and 14C arachidonic acid with cofactors, with incubation being carried out for 10 minutes at 37 degrees C. After extraction, the radioactivity of PGE2 was measured and PG synthetase activity was assayed. The apparent Km value for PG synthetase in decidua was 4.6 +/- 0.14 x 10(-6) M (n = 4), whereas that in endometrium was 4.6 +/- 1.18 x 10(-6) M (n = 3). Subsequently, kinetic studies on PG synthetase inhibitor in decidua were carried out. When sheep seminal vesicle was used as an enzyme source, the decidual supernatant showed competitive inhibition. The inhibitory substance in decidua was inactivated after incubation f...
Reproductive Biology and Endocrinology, 2016
Background: Cyclooxygenase (COX)-derived prostanoids (PGE 2, PGI 2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy. Methods: To understand the role of Ang-(1-7) in prostaglandin production in a decidualized uterus, induced by a bolus injection of sesame oil, Ang-(1-7) (24 μg/kg/h) or vehicle was then infused directly into the decidualized uterine horn using an osmotic minipump. The right horns were not injected or infused and served as nondecidualized uterine horns in both groups of animals. Results: Decidualization increased PGE 2 concentration in the uterus (0.53 ± 0.05 vs. 12.0 ± 3.2 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns); Ang-(1-7) infusion attenuated the increase of PGE 2 (12.0 ± 3.2 vs. 5.1 ± 1.3 pmol/mg protein, p < 0.01 control vs. Ang-(1-7) treated decidualized horns). The stable metabolite of PGI 2 (6-keto PGF 1α) was increased with decidualization (0.79 ± 0.17 vs. 3.5 ± 0.82 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns). Ang-(1-7) infusion attenuated the increase in 6keto PGF 1α in the decidualized horn (3.5 ± 0.82 vs 1.8 ± 0.37 pmol/mg protein, p < 0.05 control vs. Ang-(1-7) treated decidualized horns). The circulating levels of 6-keto-PGF 1a and TXB 2 were decreased by Ang-(1-7) infusion, while no difference was observed in circulating PGE 2. Although the global assessment of cleaved caspase 3 immunostaining, a marker of apoptosis, was unchanged within the Ang-(1-7) decidualized horn, there were localized decreases in cleaved caspase 3 staining in the luminal region in the decidualized uterus of Ang-(1-7)-treated rats. Conclusions: These studies show that increased local uterine Ang-(1-7) alters the uterine prostaglandin environment, possibly leading to disruptions of early events of decidualization.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2004
Prostaglandin E2 (PGE2) exerts its biological effects through 4 different receptor subtypes, EP-1, EP-2, EP-3, and EP-4. Recently we have demonstrated the importance of the prostaglandin E2 receptor subtype EP-2 in the healing of bone defects and fractures. This discovery led to the identification of CP-533,536, an EP-2 selective agonist, a promising therapeutic alternative for the enhancement of bone healing and the treatment of fractures (J Bone Miner Res 18 (2003) 2033). PGE2 has a myriad of effects throughout the body including the induction of uterine contractions, which results in termination of pregnancies. Our objective in this study was to determine the role of the EP-2 receptor and specifically that of CP-533,536, an EP-2 specific agonist, to induce uterine contractions and terminate pregnancy in guinea pigs, an animal model of human pregnancy. Preliminary experiments confirmed earlier reports that the guinea pig uterus was more sensitive than that of the rat. The guinea pig uterus contains the four PGE2 receptor subtypes, and ex vivo treatment of the uterus with PGE2 as expected causes profound uterine contractions. However, using receptor selective prostaglandin agonists including CP-533,536 we showed that the EP-1 and 3 receptors not the EP-2 receptor is responsible for the induction of uterine contractions of PGE2. Further, CP-533,536 did not antagonize the ability of PGE2 to induce uterine contractions in this model.
Prostaglandin F receptor expression in intrauterine tissues of pregnant rats
Journal of Veterinary Science, 2014
In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p ＜ 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p ＜ 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p ＜ 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p ＜ 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.