Preeclampsia and molar pregnancy are two devastating placental pathologies characterized by an immature proliferative trophoblast phenotype accompanied by excessive cell death. It is therefore of paramount importance to study the regulation of cell fate in the placenta, to gain a further understanding of the mechanisms that contribute to these diseases. In this dissertation we report that during normal placental development and in preeclampsia, Matador (Mtd), a pro-apoptotic member of the Bcl-2 family, has a dual function in regulating trophoblast cell proliferation and death. Importantly, we reveal a novel role of Mtd-L in promoting cyclin E1 expression and cell cycle progression. Of clinical importance, we also identify that both cyclin E1 and the CDK inhibitor p27, are increased in severe early onset preeclampsia. However, the inhibitory function of p27 in this pathology may be hampered due to its increased phosphorylation at Ser10, resulting in its nuclear export. Of equal importance, data presented demonstrate that placentae from severe early onset preeclampsia display a molecular profile distinct from late onset preeclampsia or intrauterine growth restricted pregnancies. In the final data chapter we demonstrate that Mtd is highly expressed in molar tissue, where it localizes to both apoptotic and proliferative cells. Our data suggests that an abundance of Mtd and cyclin E1 in conjunction with the low level of p27 may contribute to the hyperproliferative nature of the disorder. The body of work in this dissertation uncovers novel insights into the regulation of trophoblast cell fate. Importantly, the impact of Mtd on cyclin E1 to promote G1-S transition is a novel mechanism found to regulate trophoblast cell proliferation in normal and pathological placentation. Equally important is our identification of molecular differences between placental pathologies that may help to differentiate early and late onset preeclampsia, IUGR and molar pregnancy.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

No description available.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Submitted by MILENE ROCHA RIBEIRO (mrocharibeiro@yahoo.com.br) on 2018-07-12T17:13:42Z No. of bitstreams: 1 tese milene Final 2018.pdf: 2347108 bytes, checksum: e7698208bc381aa0ba18d041fd938d1b (MD5) / Approved for entry into archive by Paula Torres Monteiro da Torres (paulatms@sjrp.unesp.br) on 2018-07-13T18:00:11Z (GMT) No. of bitstreams: 1 ribeiro_mr_do_sjrp.pdf: 2347108 bytes, checksum: e7698208bc381aa0ba18d041fd938d1b (MD5) / Made available in DSpace on 2018-07-13T18:00:11Z (GMT). No. of bitstreams: 1 ribeiro_mr_do_sjrp.pdf: 2347108 bytes, checksum: e7698208bc381aa0ba18d041fd938d1b (MD5) Previous issue date: 2018-06-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O ZIKV é um vírus de RNA, não segmentado, de fita simples e sentido positivo membro da família Flaviviridae. O genoma viral possui uma arquitetura típica de flavivírus, com cerca de 11kb de comprimento, que codifica três proteínas estruturais (Capsídeo, precursor-Membrana, Envelope) e sete proteínas não-estruturais (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). Nas Américas, emergiu rapidamente após surto na ilha da Páscoa, Chile. No Brasil, o surto iniciou em 2015, aumentando consideravelmente casos de microcefalia em recém-nascidos. Aliada a esses casos, também foi observada a ocorrência de síndrome neurológica de Guillain-Barré. Essas associações transformaram o impacto da transmissão e infecções por ZIKV em uma preocupação de saúde pública global. O vírus é transmitido principalmente pelos mosquitos do gênero Aedes, que possuem ampla distribuição e apresentam grandes adaptações a ambientes urbanos. Além de transmissão vetorial, pode ser transmitido via sexual e materno-fetal. O objetivo deste trabalho foi comparar as infecções por uma cepa contemporânea de ZIKV com DENV2 em modelo de explantes de placenta humana a termo, bem como quantificar expressão de citocinas, interferons do tipo I, II e III e marcadores de apoptose induzida via infecção viral. Os resultados demonstram que os explantes da placenta a termo são permissivos e apoiam a infecção por ZIKV. A quantificação da carga viral entre infecções ZIKV e DENV2 foram similares. No entanto, DENV2 apresentou decréscimo na liberação de carga viral em 24 horas pós-infecção. A cinética da replicação viral coincidiu com a expressão de citocinas pró-inflamatórias e o aumento de apoptose no tecido infectado. Clivagem de caspase 3 foi parcialmente dependente de TNF- α e o tratamento com Anti-TNF-α diminuiu significativamente essa ativação mediada por infecção viral. Cumulativamente, este modelo demonstra que os tecidos placentários humanos são alvo de infecção por ZIKV e que a infecção é patogênica para o tecido placentário. Palavras-chave: placenta humana, Flavivírus, explantes, apoptose, interferon, caspase 3. / ZIKV is a non-segmented, single-stranded, positive-sense RNA virus and a member of the Flaviviridae family. Its genome has a typical 11 kB-long flavivirus architecture that encodes three structural proteins (Capsid, PrecursorMembrane, Envelop) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). In the Americas, the viruses emerged rapidly after outbreak on Pascoa Island, Chile. The outbreak reached Brazil in 2015, substantially increasing cases of microcephaly in newborns. In addition to microcephaly, cases associated with neurological diseases such as GuillainBarré syndrome have made ZIKV a global public health concern. The virus is mainly transmitted by mosquitoes of the genus Aedes, which are widely distributed and which have adapted well great to urban environments. In addition to vector transmission, ZIKV can be transmitted via sexual and maternal-fetal routes, the virus has been isolated is from sperm, amniotic fluid and central nervous systems of stillborn fetuses. The goal of this report was compare ZIKV-infected to DENV2 in full-term human placenta explant model. Quantify expression of cytokines, type I, II and III interferons and markers of induced-apoptosis by viral infection. The results demonstrated that full-term placenta explants are permissive and support ZIKV infection. Viral loads in ZIKV and DENV2 infections were similar. However, DENV2 presented a decrease in viral load release at 24 hours post infection (h.p.i). The kinetics of viral replication coincided with the expression of proinflammatory cytokines and the increase of apoptosis in the infected tissue. Apoptosis was partially dependent on TNF-α. Anti-TNF-α treatment significantly decreased the activated-caspase 3 mediated viral infection. Cumulatively, this model demonstrates that human placental tissues are targets of ZIKV-infection and that the infection is pathogenic to placental tissue.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Per- and polyfluoroalkyl substances (PFAS) encompass a large group of manufactured compounds that have been used in various production processes such as food packaging, commercial products, workplaces, homes, water supplies, and food. PFAS are persistent, resistant to degradation, and can bioaccumulate. Although an exposure limit that predicts adverse health effects has yet to be determined, the Center for Disease Control and Prevention’s 2015-16 health survey found average blood levels of 4.72 ng/ml for PFOS and 1.56 ng/ml for PFOA. The objective of this research was to evaluate the use of laminar flow tandem mass spectrometry following solid phase extraction (SPE) using weak anion exchange (WAX) properties on the detection and quantitation of PFAS compounds. Seven-point calibration standards applied to this research were prepared using certified reference materials (Wellington Laboratories, Ontario, CA), and calibrators were run without sample extraction. The concentrations varied slightly based on the PFAS analyte of interest. All samples and quality controls were prepared by spiking certified reference material (Wellington Laboratories) into pooled human serum (BioIVT, Westbury, NY, USA). A laminar flow QSight®220 ultra-high pressure liquid chromatography-tandem mass spectrometer (LC-MS/MS, PerkinElmer, Waltham, MA, USA) was equipped with a Selectra C18 100 x 2.1mm x 3μm (UCT, Bristol, PA, USA) column with a Brownlee C18 delay column (PerkinElmer) and followed the LC-MS/MS parameters developed for the method. Extraction was accomplished using a WAX SPE column (UCT, ECWAX053) by first conditioning the columns with 1 mL of methanol (Fisher Scientific, Fair Lawn, NJ, USA) followed by 1 mL of 100 mM pH 7 phosphate buffer (Acros Organics, Geel, Belgium, EU). Samples were loaded onto the column at a rate of 1-2 mL/min. The SPE cartridges were washed with 1 mL of 100 mM pH 7 phosphate buffer and 1 mL of millipore water (Millipore Milli- Q Ultrapure Type 1 water system, Millipore Sigma, Burlington, MA, USA), then dried under full flow for 5 minutes. Elution was carried out with 2.5mL of a 98:2 methanol: OptimaTM grade ammonium hydroxide (Fisher Scientific) solution. The eluted samples were then evaporated to dryness using a MULTIVAP® Nitrogen Evaporator (Organomation,Berlin,MA,USA) at 55°C and 5psi. All samples were reconstituted in 100 μL of a 96:4 methanol:water solution. The parameters assessed followed Academy Standards Board Standard 036: Standard Practices for Method Validation in Forensic Toxicology, including matrix interferences, limit of detection (LOD), limit of quantitation (LOQ), a recovery study, and a calibration model. The results of the study were gathered from the following eleven analytes: PFBA, PFBS, PFHxA, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnA, and PFDoA. Depending on the analyte, a lower LOQ was established at 0.16 – 1.75ng/mL and an upper LOQ at 43.75 – 51.41 ng/mL. Based on the established linear calibration model an LOD in the range of 0.11 - 0.51 ng/mL was achieved. All eleven PFAS analytes showed an acceptable bias of ±20%. All analytes showed a between-run precision (%CV) in an acceptable range of ±20%. No matrix interferences were detected. The average recovery for SPE ranges from 77.64- 104.73% with recovery of 77.64% for PFBS, 83.89% for PFBA, and 95.64-104.73% for PFHxA, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnA, and PFDoA. Utilizing the UCT WAX SPE column, good recovery for the PFAS compounds was demonstrated. Further, the extraction technique was efficient for high throughput analysis with the extraction time comparable to other traditional SPE methods. The total analytical run time of 11 minutes using the QSight®220 coupled with the UCT Selectra C18 100 x 2.1mm x 3μm column allowed for adequate re-equilibration and system washes to prevent carryover and contamination of these persistent pollutants with excellent chromatography. Having the ability to efficiently and accurately quantify PFAS compounds in biological matrices will allow for better understanding of prevalence, bioaccumulation in biological matrices, and will aid in understanding how these concentrations relate to various health outcomes.

Le Bisphénol A (BPA) est un perturbateur endocrinien dont les effets développementaux observés chez les rongeurs soulèvent la question du risque pour la santé humaine relatif à une exposition fœtale au BPA. L’objectif de cette thèse est de déterminer les mécanismes toxicocinétiques impliqués dans l’exposition fœtale au BPA. La caractérisation in vivo dans un modèle intégratif ovin des expositions maternelles et fœtales au BPA et à ses métabolites ont permis d’identifier le transfert placentaire et le métabolisme fœto-placentaire comme les déterminants majeurs de l’exposition fœtale au BPA. Le transfert bidirectionnel du BPA à travers le placenta humain se fait par diffusion passive conduisant à un rapport maximal des concentrations plasmatiques de BPA libre entre le fœtus et sa mère de 1. En revanche, la perméabilité placentaire du BPA-G est très limitée, en particulier dans le sens materno-fœtal. Les activités de conjugaison hépatique du BPA ont été faibles chez le fœtus ovin à un stade précoce de gestation et ont augmenté au cours du développement. Par ailleurs la réactivation des conjugués du BPA mise en évidence ex vivo dans les gonades fœtales ovines pourrait conduire à une exposition locale au BPA actif. L’ensemble de ces données suggère que le début de la gestation pourrait représenter une fenêtre critique d’exposition au BPA / Bisphenol A (BPA) an endocrine disruptor interfering with developmental processes in rodents, raises the question of risk for human health related to fetal exposure to BPA. The goal of this work was to determine the toxicokinetic mechanisms involved in fetal exposure to BPA. The disposition of BPA and its metabolites in the maternal-placental-fetal unit in an in vivo ovine model enabled us to identify the placental transfer and the fetal-placental metabolism as the major determining factors of fetal exposure to BPA. Bidirectional placental transfer of BPA occurs by passive diffusion leading to a ratio of free BPA between the fetal and maternal plasma concentrations of about 1. By contrast, the permeability of BPA-G is very limited, particularly in materno-to-fetal direction. The hepatic conjugation activities were very low in ovine fetus at an early stage of development and increased throughout pregnancy. Hydrolysis of BPA conjugates observed ex vivo into fetal ovine gonads could lead to local exposure to native BPA. Altogether, these results suggest that the early stage of pregnancy is a critical window of exposure for the developing fetus

Le placenta assure les échanges materno-fœtaux et possède une fonction endocrine autonome. Les hormones placentaire lactogène (hPL) et chorionique gonadotrope (hCG) sont synthétisées par le syncytiotrophoblaste. A ce jour, les mécanismes impliqués dans le contrôle de la sécrétion de ces deux hormones ne sont pas connus. In vitro, l’influx d’ions Ca2+ entraîne une augmentation immédiate et soutenue de la libération d’hPL et d’hCG à partir d’explants de placentas à terme. En outre, l’élévation de la concentration extracellulaire en albumine, principale protéine maternelle circulante en contact direct avec le trophoblaste, stimule de manière immédiate et transitoire la libération d’hPL et d’hCG.<p><p>L’objectif de nos travaux a été de vérifier la spécificité de l’activité sécrétagogue de l’albumine au niveau du placenta, de caractériser les messagers cellulaires potentiellement impliqués dans la libération d’hPL et d’hCG, et de définir l’interaction entre l’albumine et le trophoblaste, en utilisant des explants provenant de placentas humains à terme.<p> <p>Nos travaux démontrent que la riposte sécrétoire à l’albumine (5%, m/v) est largement mimée par d’autres agents colloïdaux (dextran et polygéline). Cette stimulation colloïdale de la libération d’hPL et d’hCG impliquerait une mobilisation de Ca2+ à partir de réserves intracellulaires. L’intervention de 3 messagers cellulaires a été envisagée: les IPs/DAG, l’AMPc, et le GMPc. Le fluorure de sodium, la forskoline, ou le nitroprussiate sodique, activateurs connus de la production respective des IPs, de l’AMPc, et du GMPc, augmentent de manière significative les taux placentaires de chacun de ces messagers, sans toutefois affecter la libération d’hPL ou d’hCG. De plus, l’élévation de la concentration extracellulaire en albumine (5%, m/v) ne modifie pas les taux des IPs, de l’AMPc et du GMPc dans les explants placentaires, tandis qu’elle stimule la sécrétion hormonale. Ces systèmes de signalisation, bien que fonctionnels au niveau du trophoblaste, ne joueraient donc pas un rôle majeur dans la régulation de la libération d’hPL et d’hCG. <p><p>Nos résultats mettent en évidence une internalisation rapide d’albumine marquée, avec de l’125I ou de la fluorescéïne, dans le syncytiotrophoblaste. Une large fraction de cette albumine est recyclée, intacte, vers la circulation maternelle selon un processus sensible à l’abaissement de la température et indépendant du cytosquelette. L’albumine marquée restant dans les explants placentaires est partiellement dégradée. Trois mécanismes ont été envisagés pour expliquer ces mouvements d’entrée et de sortie de l’albumine au sein du placenta humain: l’endocytose médiée par l’albondine via les caveolae, le système des coated pits clathrine-dépendant, et l’endocytose médiée par la mégaline. Par immunohistochimie, nous avons montré que, dans le tissu placentaire, la caveoline-1, protéine caractéristique des caveolae, est localisée uniquement dans l’endothelium des capillaires fœtaux. La clathrine, au niveau des coated pits, et la mégaline se trouvent au contraire dans le syncytiotrophoblaste. La méthyl-b-cyclodextrine et l’hydrochlorure de chlorpromazine, inhibiteurs d’une endocytose dépendant de la clathrine, réduisent significativement l’internalisation placentaire de l’albumine marquée. Par contre, le DIDS ou le NPPB, susceptibles de perturber l’endocytose médiée par la mégaline, n’affectent pas la captation d’albumine marquée par les explants placentaires. L’albumine pénétrerait donc dans le syncytiotrophoblaste principalement par un processus clathrine-dépendant. La mégaline ne jouerait ici qu’un rôle mineur dans l’entrée de la protéine. Un tel processus de recyclage de l’albumine pourrait être similaire à celui décrit pour les immunoglobulines G au niveau du syncytiotrophoblaste.<p><p>Ces mouvement d’entrée et de sortie de l’albumine ne semblent pas associés à la stimulation de la libération d’hPL et d’hCG par l’albumine. Ils pourraient par contre participer significativement, étant donné leur ampleur, à la nutrition fœtale. L’albumine est en effet un transporteur notoire d’ions et d’acides gras, molécules qui pourraient être acheminées au fœtus via le phénomène de recyclage placentaire de l’albumine mis en évidence par ce travail. /<p><p>The human placenta is the site of all maternal-fetal exchanges, and is also an active endocrine organ. Placental lactogen (hPL) and chorionic gonadotrophin (hCG) hormones are synthesized by the syncytiotrophoblast. So far, the mechanisms involved in the regulation of both hormones secretion remain elusive. In vitro, calcium inflow causes an immediate and sustained rise in the hPL and hCG releases from human term placenta explants. Moreover, increasing the extracellular concentration of albumin, the major maternal plasma protein in direct contact with the human trophoblast, stimulates the hPL and hCG releases in an immediate and transient way.<p><p>Our study have aimed to check the specificity of this secretory effect of albumin, to investigate the potential cellular messengers involved in the hPL and hCG releases, and to define the interaction between albumin and the throphoblast layer, using human term placenta explants.<p><p>Our results indicate that the triggering effect of albumin (5%, w/v) is largely mimicked by two other colloidal agents (dextran and polygelin). This “colloidal” stimulation of the hPL and hCG releases would involve the mobilization of calcium from intracellular pools. Three cellular messengers have been considered to mediate this process: the IPs/DAG, the cAMP, and the cGMP. Sodium fluoride, forskolin, or sodium nitroprusside, known activators of respectively the IPs, cAMP, and cGMP production, significantly increase the placental content of each of those messengers, without modifying the hPL and hCG releases. In addition, raising the extracellular concentration of albumin does not cause any change in the placental level of IPs, cAMP, and cGMP, while stimulating the hormonal release. These three signaling pathways are thus functional in human term trophoblast but do not appear to significantly modulate the hPL and hCG secretions. <p><p>Our findings show that albumin, labeled with 125I or with fluorescein, is rapidly internalized into the syncytiotrophoblast. Thereafter, the intact protein is largely recycled to the maternal circulation, through a temperature-sensitive and cytoskeleton-independent process. The labeled albumin remaining in placental explants is partially degraded. Three different mechanisms could participate to the albumin entry into the human placenta: the albondin-mediated endocytosis via the caveolae, the clathrin-dependent coated pits system, and the megalin-mediated endocytosis. Using immunohistochemistry, caveolin-1, marker of the caveolae, is localized in the endothelium of the fetal capillaries and not in the syncytiotrophoblast. By contrast, clathrin and megalin are observed only in the syncytiotrophoblast. Methyl-b-cyclodextrin, and chlorpromazine hydrochloride, known inhibitors of the clathrin-dependent endocytotic process, significantly reduce the placental uptake of labeled albumin. On the other hand, DIDS or NPPB, able to perturb the megalin-mediated endocytosis, do not affect the labeled albumin uptake. Thus, albumin seems to be internalized into the syncytiotrophoblast mainly through a clathrin-dependent mechanism. Megalin would only play a minor role in this process. Such movements of albumin in the human placenta may be similar to the recycling process reported for IgG at that site.<p><p>The placental apical recycling of albumin is not associated to the albumin triggering effect on the hPL and hCG releases. This quantitatively significant internalization process may participate to the fetus’ nutrition. Indeed, Albumin carries ions and fatty acid, which could be brought to the fetus via the protein recycling evidenced by our study.<p><p><p> <p> / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

L’implantation embryonnaire repose sur une synchronisation spatio-temporelle entre un placenta fonctionnel et un endomètre réceptif. La réceptivité endométriale requiert la différenciation des cellules stromales en cellules déciduales sous l’effet des hormones ovariennes (œstrogènes et progestérone). Le placenta est un organe transitoire constitué de deux types cellulaires. Le cytotrophoblaste villeux est responsable des échanges fœtaux maternels et de la fonction endocrine du placenta. Le cytotrophoblaste extravilleux présente des propriétés invasives et assure ainsi l’ancrage du placenta dans l’endomètre maternel. Un dialogue paracrine complexe entre les cellules placentaires et endométriales s’établit au cours des premières étapes de l’implantation.L’adiponectine est une adipokine produite majoritairement par le tissu adipeux. Elle contrôle le métabolisme glucido-lipidique et joue le rôle d’hormone insulino-sensibilisatrice. Dans de nombreux tissus, l’adiponectine exerce des effets anti-prolifératifs, pro-invasifs et pro-différenciants. L’adiponectine et ses récepteurs ADIPOR1 et ADIPOR2 sont présents à l’interface fœto-maternelle. Le placenta et l’endomètre sont donc des tissus cibles de l’adiponectine.Au cours de ce travail, nous nous sommes intéressés aux effets directs de l’adiponectine à l’interface foeto-maternelle au cours du premier trimestre de grossesse.Dans une première partie, nous avons observé que l’adiponectine exerce des effets anti-différenciants et anti-invasifs dans les cellules stromales endométriales.Dans un second temps, nous avons démontré que l’adiponectine favorise la production de glycogène dans les cellules déciduales. Inversement, l’adiponectine semble limiter l’entrée du glycogène dans les cellules placentaires. Ces résultats démontrent que l’adiponectine pourrait contrôler la nutrition histiotrophe du foetus.Dans une dernière partie, nous avons observé que l’adiponectine diminue l’expression des transporteurs de nutriments et exerce une action pro-apoptotique dans le trophoblaste villeux. Ces derniers résultats pourraient permettre de mieux comprendre le rôle de l’adiponectine dans les pathologies placentaires telles que le retard de croissance intra-utérin qui se caractérise par une diminution du poids foetal et une augmentation de l’apoptose des cellules trophoblastiques.L’ensemble de ces résultats montre que l’adiponectine est un acteur clé du dialogue foeto-maternel au cours de la grossesse précoce en contrôlant la maturation d’un endomètre fonctionnel et en régulant les échanges nutritifs transplacentaires. / Embryo implantation requires a spatiotemporal synchronization between a functional placenta and a receptive endometrium. Endometrium receptivity based on the differentiation of stromal cells into decidual cells, under the influence of ovarian hormones (estrogens and progesterone). The placenta is a transient organ composed of two cell types. Villous trophoblast ensures fetal-maternal exchanges and the endocrine functions. Extravillous trophoblast acquire an invasive phenotype resulting in the placenta anchoring in the endometrium. Then, a complexe paracrine dialog between placental cells and endometrial cells is established during the first stages of the embryo implantation.Adiponectin is an adipokine predominantly produced by the adipose tissue. This cytokine has an important role in the control of energy metabolism and displays an insulin-sensitizing action. In some cell types, adiponectin limits proliferation, but promotes invasion and differentiation. Adiponectin and its receptors ADIPOR1 and ADIPOR2, are expressed at the fetal-maternal interface. Thus, endometrium and placenta are adiponectin targets.In this work, we aimed to determine adiponectin direct effects at the human fetal maternal interface during the first trimester of pregnancy.In a first part, we observed that adiponectin limits differentiation and invasion in endometrial stromal cells.In a second part, we showed that adiponectin promotes glycogen production by decidual cells. Conversely, adiponectin seems to limit glycogen uptake by placental cells. These results demonstrate that adiponectin could regulate histiotrophic nutrition to the fetus.In a last part, we demonstrated that adiponectin down-regulates the expression of nutrient transporters and promotes apoptosis in villous trophoblast. These last results could help to better understand the adiponectin roles in some placental pathologies, as intrauterine growth restriction, characterized by a decreased fetal weight and a enhanced trophoblastic apoptosis. Altogether, these results demonstrate that adiponectin is a key regulator of the fetal-maternal dialog by controlling the differentiation of a functional endometrium and by regulating transplacental nutrient exchanges.