scholarly journals Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses

2018 ◽  
Vol 7 (5) ◽  
pp. 749-761 ◽  
Author(s):  
Yao Ye ◽  
Aurelia Vattai ◽  
Nina Ditsch ◽  
Christina Kuhn ◽  
Martina Rahmeh ◽  
...  

Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy, and it can stimulate inflammatory reactions via prostaglandin E2 receptor 3 (EP3). However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether EP3 signaling is involved in the mechanism of uRPL. Via immunohistochemistry we could show that the expression of cyclooxygenase-2, EP3 and G protein alpha inhibitor 1 (Gi1) was enhanced in the decidua of the uRPL group in comparison to the control group in first-trimester placentas. In vitro, we demonstrated that sulprostone (an EP1/EP3 agonist) inhibited the secretion of beta-hCG and progesterone in JEG-3 cells and the secretion of beta-hCG in HTR-8/SVneo cells while it induced the expression of plasminogen activator inhibitor type 1 in JEG-3 cells. In addition, PGE2/sulprostone was able to stimulate the expression of Gi1, phosphorylated-extracellular signal-regulated kinases 1/2 (p-ERK1/2) and p53. L-798,106 (an EP3-specific antagonist) suppressed the expression of EP3 and p-ERK1/2 without affecting the secretion of beta-hCG. Elevated activation of EP3 signaling in first-trimester placentas plays an important role in regulating the inflammatory microenvironment, the hormone secretion of extravillous trophoblasts and the remodeling of extracellular matrix in the fetal-maternal interface. L-798,106 might be a ‘potential therapeutic candidate’ for the treatment of uRPL.

2018 ◽  
Vol 46 (9) ◽  
pp. 953-959
Author(s):  
Iwona Szymusik ◽  
Przemyslaw Kosinski ◽  
Katarzyna Kosinska-Kaczynska ◽  
Damian Warzecha ◽  
Anetta Karwacka ◽  
...  

AbstractObjectives:The aim of this study was to determine if the levels of biochemical aneuploidy markers inin vitrofertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations.Methods:This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM).Results:The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%).Conclusions:The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.


2020 ◽  
Vol 29 ◽  
pp. 096368972092505
Author(s):  
Yuan Qiao ◽  
Helena Kolibaba ◽  
Yukiko Mori ◽  
Tao Liu ◽  
Huijun Chen ◽  
...  

This paper aimed to evaluate whether human cytomegalovirus (HCMV) infection in extravillous cytotrophoblasts (EVT) could shift the balance between regulatory T (Treg) and T-helper type 17 (Th17) cells in vitro. In this study, primary EVT isolated from first trimester placental tissues were infected with HCMV, and conditional media were harvested after cultivation for 72 h. T lymphocytes were cultured in the presence or absence of HCMV-infected conditional media. The frequencies of Th17 or Treg cells from HCMV group were significantly lower or higher than those from the control group, with the expression of corresponding key cytokines at both messenger ribonucleic acid and secretion levels, respectively. The ratio of Treg to Th17 cells was significantly lower in HCMV group than that in control group ( P < 0.01). In conclusion, tiled Th17/Treg balance at maternal–fetal interface exists after HCMV infection.


2015 ◽  
Vol 6 (4) ◽  
pp. 97-104
Author(s):  
Arina Yurevna Malenova ◽  
Irina Gennadevna Kytkova

Research objective - studying of features of the relation to pregnancy, the child, motherhood of women in IVF situation. Selection: 100 married pregnant women aged from 28 till 42 years (the first pregnancy of the first trimester, complications in the anamnesis isn't present) representing two groups on 50 people: 1) after artificial insemination (empirical group); 2) in a situation natural pregnancy (control group). The leading motives of pregnancy, types of the attitude towards themselves, pregnancies, to the child, people around, the prevailing installations in the sphere of the family relations, features of representation of future mothers about themselves and "the ideal parent" are defined by testing. Distinctions in all respects with women from control group are found. It is established that in vitro fertilisation the high level of readiness for motherhood according to its motivational characteristics is observed. Prevalence of constructive motives of pregnancy against concern in the health and aspirations to meet social expectations is revealed. The leading types of a gestational dominant are optimum and euphoric, the hypertrophied positive emotional background of pregnancy is observed. In the future of a bike probability the dependent relations with the child, preference of the sponsoring or authoritative style of family education. Revaluation of own parental qualities when comparing with image of ideal mother is observed. Results allow to carry women to the group of risk demanding psychological maintenance before and after the childbirth.


2019 ◽  
Author(s):  
Guangyi Zhao ◽  
Jianying Zhang ◽  
Daibang Nie ◽  
Yiqin Zhou ◽  
Feng Li ◽  
...  

AbstractMechanical overloading is a major cause of tendinopathy, but the underlying pathogenesis of tendinopathy is unclear. Here we report that high mobility group box1 (HMGB1) is released to the tendon extracellular matrix and initiates an inflammatory cascade in response to mechanical overloading in a mouse model. Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene and a specific inhibitor of HMGB1, the tendon’s inflammatory reactions. Also, while prolonged mechanical overloading in the form of long-term intensive treadmill running induces Achilles tendinopathy in mice, administration of GL completely blocks the tendinopathy development. Additionally, mechanical overloading of tendon cells in vitro induces HMGB1 release to the extracellular milieu, thereby eliciting inflammatory and catabolic responses as marked by increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 (MMP-3) in tendon cells. Application of GL abolishes the cellular inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as a key molecule that is responsible for the induction of tendinopathy due to mechanical overloading placed on the tendon.


2021 ◽  
Vol 8 ◽  
Author(s):  
Deborah Carbonera Guedes ◽  
Manuel Hospinal Santiani ◽  
Joyce Carvalho ◽  
Carlos Ricardo Soccol ◽  
João Carlos Minozzo ◽  
...  

Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptide mix generated the IFN-γ, IL-12, IL-4 and TGF-β that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.


2005 ◽  
Vol 17 (9) ◽  
pp. 79
Author(s):  
A. Charles ◽  
S. Hisheh ◽  
D. W. R. Kam ◽  
A. M. Dharmarajan

Pro-apoptotic genes have a role in the differentiation process in the placenta leading to the fusion of cytotrophoblast cells to form the protective syncytiotrophoblast layer. The mechanisms of apoptosis in the human placenta are not clearly understood. However, a major placental apoptotic-signalling pathway is known to involve the caspases. Caspase-14 is the most recently discovered member of the caspase family members and has not previously been examined in the human placenta. The aim of the present study was to detect caspase-14 in the human placenta and study its role in apoptosis. Human placentae were collected from first trimester and term gestation. The study consisted of two parts. In the first part, first trimester and term placentae were assessed for caspase-14 by western blotting and mRNA analysis and localised with immunohistochemical studies. In the second part, apoptosis in first trimester placenta was inhibited in an in-vitro model of explant villi culture with superoxide dismutase (SOD) treatment and the genes assessed. The first study demonstrated caspase-14 to be a cytoplasmic protein localised in the cytotrophoblast cells, the mesenchyme and in the syncytiotrophoblast of the first trimester. In the term placenta, caspase-14 was expressed weakly in the syncytiotrophoblast. The immunostaining data suggest a higher expression of caspase-14 in the first trimester compared to the term placenta, and this observation was later confirmed by western blot analysis. Using the SOD in-vitro explant culture model, no significant difference in the caspase-14 protein levels were seen in either the SOD or control group. This novel study demonstrates for the first time that caspase-14 protein and mRNA are present in the human placenta. The function of caspase-14 in the human placenta is unclear.


1971 ◽  
Vol 68 (2) ◽  
pp. 355-362 ◽  
Author(s):  
F. Hertelendy

ABSTRACT Hemisected rat anterior pituitaries were incubated in KRB (pH 7.4) containing glucose (1 mg/ml) and BSA (1 mg/ml) and the release of growth hormone (GH) was measured by radioimmunoassay. Prostaglandin E1 and E2 (1 μg/ml each) increased GH concentration in the medium by 298 % and 266 % respectively over controls during a one-hour incubation period. On molar basis prostaglandins proved to be at least a thousand times more potent stimulants of GH secretion than theophylline or dibutyryl cyclic AMP. This response was drastically reduced by preincubating the pituitary explants in the presence of EGTA in a calciumfree medium. Addition of calcium (1 mm) restored the relative GH response to PGE1 though the absolute amount of GH released was considerably less than that observed without EGTA treatment. Hormone secretion was potentiated by high concentration of K+ (54 mm) which in itself significantly stimulated GH release. 2,4-Dinitrophenol almost completely abolished PGE1 stimulated GH release indicating that the latter is an energy dependent phenomenon. The possible mechanism by which prostaglandins stimulate GH secretion and the interaction of ions in the secretory mechanism are discussed.


1997 ◽  
Vol 4 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Daniel Hayoz ◽  
Do-Dai Do ◽  
Felix Mahler ◽  
Jürgen Triller ◽  
François Spertini

Purpose: Nonspecific inflammatory reactions characterized by local tenderness, fever, and flu-like discomfort have been seen in patients undergoing endoluminal graft placement in the abdominal aorta or the femoral arteries. We undertook a study to assess the clinical and laboratory parameters of this inflammation. Methods: Ten patients with femoropopliteal artery (n = 9) or aortic (n = 1) lesions were treated with EndoPro System 1 stent-grafts made of nitinol alloy and covered with a polyester (Dacron) fabric. Eleven patients implanted with a bare nitinol stent served as the control group. Results: In the stent-graft group, four patients showed clinical signs of acute inflammation manifested by fever and local tenderness. Three of these patients suffered thrombosis of the stent-grafts during the first month of follow-up. Plasma levels of interleukin-1β and interleukin-6 in all stent-graft patients were markedly increased 1 day after intervention (7.3 ± 2.8 versus 90.2 ± 34.1 pg/mL and 15.6 ± 5.8 versus 175.5 ± 66.3 pg/mL, respectively; p < 0.01). This was followed by an increase in fibrinogen (3.0 ± 0.2 versus 5.0 ± 0.2 g/L; p < 0.05) and C-reactive protein (14.6 ± 3.3 versus 77.5 ± 15.0 mg/L; p < 0.01) at 1 week. No direct correlation between the inflammatory markers and symptoms could be found. In vitro analysis showed that individual components of the stent-graft did not activate human neutrophils, whereas the intact stent-graft itself induced a marked neutrophil activation. Conclusions: The component of the self-expanding stent-graft responsible for the nonspecific inflammatory reaction was not identified in this study. It is likely that the stent-graft itself or some as yet unrecognized element of the device other than the Dacron fabric or metal alloy may be a potent in vivo inducer of cytokine reaction by neutrophils.


Author(s):  
Ann Abdel Kader ◽  
Radwa Azmy ◽  
Eman A. Maher ◽  
Basma Bahgat El Sayed ◽  
Alshaimaa Sobhi Khalil ◽  
...  

Abstract Background Statin-induced myopathy is the most common adverse effect of statins. Bee venom provides a potential mean of controlling immune responses and inflammatory reactions; the proposed mechanisms for statin-induced myopathy. Objective The present study aimed at clarification of the role of the bee venom in prevention of statin-induced myopathy. Materials and methods It was carried out on 30 Sprague-Dawley female rats. Rats were randomly classified into 3 groups: control group, statin group which received statins for 2 weeks, and venom group that was exposed to alternate day actual bee sting concurrent to statins administration for 2 weeks. Quantitative electromyography (QEMG) was performed as well as serum creatine kinase (CK) and cholesterol levels, in addition to in vitro muscle contractility tests. Results QEMG and contractility tests showed significant changes in the statin group compared to both control and venom groups. Serum cholesterol level decreased with increase in CK levels in the statin and venom groups compared to controls; however, the CK level was significantly lower in the venom group as compared to the statin group. Conclusion Bee venom therapy offers a simple and available means of prophylaxis against the myopathic effects induced by statins in animal model. However, it partly restricts the therapeutic effect of statins.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Yu ◽  
Tong Qiao ◽  
Liping Hua ◽  
Shuanghang Liu ◽  
Xinzhe Zhao ◽  
...  

Inhibin (INH) and anti-Müllerian hormone (AMH) are essential in ovarian folliculogenesis and play an inhibitory role in mammalian fertility. However, the interactive effect of INH and AMH on the animal reproduction remains unknown. This study aimed to determine the possible interaction and synergy between INH and AMH in steroidogenesis by primary granulosa cells, and investigate their synergistic effect on fertility in mice. In in vitro granulosa cell culture system, we found that the treatment of either INHA or AMH had no significant effect on basal estradiol and progesterone production, whereas both significantly attenuated FSH-induced steroid hormone secretion. Importantly, combined treatment with INHA and AMH showed additive inhibitory effect on FSH-induced estradiol and progesterone production, accompanying a significant downregulation in the expression of FSH-stimulated CYP19A1, HSD3B, CYP11A1, StAR transcripts. The interrelationship of INH and AMH combinations was further investigated through active immune neutralization strategy. Female mice were immunized against INH and AMH eukaryotic expression plasmids, and the litter size was recorded after successfully mating. We observed that both INH and AMH plasmids were able to induce either anti-AMH or anti-INH antibodies in the immunized mice. In comparison with the control group, co-immunization with INH and AMH plasmids induced higher levels of estradiol, resulting in more litter size. Moreover, there was no significant difference on the offspring's weight between each group. Collectively, the results of the present study suggest that INH and AMH have synergistic effect in regulating steroidogenesis and the litter size in mice.


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