Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells

<p>Abstract</p> <p>Background</p> <p>In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation.</p> <p>Results</p> <p>We showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up-regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down-regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation.</p> <p>Conclusion</p> <p>Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation.</p

Développement d'un modèle numérique de prédiction des émissions d'oxydes d'azote pour la simulation aux grandes échelles de chambres de combustion aéronautiques

Cette thèse est consacrée à l amélioration des capacités de prédiction des émissions d oxydes d azote (NO et NO2) des foyers de combustion aéronautiques. Les travaux, exclusivement numériques, consistent d abord dans une étude de la cinétique chimique responsable des émissions polluantes. Cetteétude conduit à l écriture d un modèle, nommé NOMANI (pour Nitrogen Oxide emission model with one-dimensional MANIfold), basé sur l approche PCM-FPI (pour Presumed Conditional Moments - Flame Prolongation of ILDM) avec une variable de progrès additionnelle afin calculer l avancement de la chimie azotée une fois la chimie carbonée à l équilibre. Différentes validations sur des configurations laminaires simples puis des flammes de laboratoire de Sandia sont présentées. Les résultats en terme de structure de flamme et d'émission de monoxyde d azote sont confrontés aux mesures expérimentales. Le dernier volet de ces travaux, disponible uniquement dans la version confidentielle du manuscrit, consiste dans le développement d un modèle de prédiction de polluants associé au modèle TF-LES (pour Thickening Flame for Large Eddy Simulation). Le modèle développé est ensuite appliqué à des calculs d une chambre de combustion aéronautique.This thesis is focused on the prediction capabilities of nitrogen oxides (NO and NO2) for numerical tools applied to aeronautical combustion chambers. The modeling work is based on a study of the chemical kinetic that produced the pollutant emissions. This study leads to a model, called NOMANI (Nitrogen Oxide emission model with one-dimensional MANIfold), based on PCM-FPI (Presumed Conditional Moments - Flame Prolongation of ILDM) with an additional progress variable to compute the NO evolution once the carbon chemistry is at the equilibrium. Several benchmarks and test-cases (laminar and turbulent flames) are gathered in this study : Sandia flame have been computed and satisfactory comparisons with measurements are obtained. The last part of this work, only available in the confidential version of the manuscript, is the development of a model to predict pollutant associated with the model TF-LES (for Thickening Flame for Large Eddy Simulation). This model is then applied to computations of a aeronautical combustion chambers.ROUEN-INSA Madrillet (765752301) / SudocSudocFranceF

Effects of adiponectin on human trophoblast invasion

International audienceAdiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion