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Trophoblasts --- Pregnancy Complications, Neoplastic

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The MAGE-A protein belong to a family of proteins which are present in many human cancers of different histological types. However, these proteins are absent in most healthy tissues, except for testis and placenta.
Since the functions of proteins MAGE-A are poorly known, the objective of my report was to characterize them in the human trophoblastic cells, that have the characteristics to be highly invasive. Implantation of the foetus realized by the trophoblast in the maternal endometrium present resemblances to the invasive capacities of the cancer cells. The inhibition of the constitutive expression of proteins MAGE-A in trophoblasts could allow us to determine if their role is to influence the migration and the invasive behaviour of these cells. Then, we could evaluate if MAGE-A proteins are involved in the proliferation and the metastasis properties of the cancer cells.
Initially, it was essential to start by characterizing the expression of MAGE-A genes in the trophoblasts by quantitative or qualitative PCR, in order to identify the genes of this family which were to be targeted specifically. The results obtained agree with those of the previous studies and showed that gene MAGE-A10 is most strongly and more frequently expressed in primary cultures of early trophoblastic cells. By contrast, choriocarcinoma cells lines derived from trophoblastic tumors had a pattern of expression of MAGE-A genes was different from that of healthy trophoblasts obtained by primary cultures of first trimester placenta. This pattern was very similar to that observed in other types of tumors, such as melanoma and lung cancer.
In the second place, a pool of interfering RNA targeting specifically MAGE-A10 transcripts was tested in melanoma cell line LB373-MEL strongly expressing MAGE-A10. The most effective interfering RNA was highlighted by techniques of quantitative PCR and Western Blot. Primary cultures of humantrophoblasts were transfected with this interfering RNA. The results of the quantitative PCR and the Western Blot showed a reduction in the level of MAGE-A10 transcripts at most by factor 5 in the presence of the interfering ARN. These transfected trophoblastics cells were subjected to migration and invasion assays in order to study the consequences of this inhibition. We did not observe any migration of transfected or untransfected trophoblasts. The invasion tests revealed that there was a reduction by a factor 3 in the invasive capacities of the cells treated with a control interfering RNA or the interfering RNA targeting MAGE-A10 compared to the untreated trophoblastic cells. The same effect was observed when melanoma cell line ME248.3 that expresses mostly MAGE-A10, was treated with interfering RNA.
Although, these preliminary experiments suggest that MAGE-A10 could be involved in the invasion capabilities of the trophoblastic cells, additional experiment are needed to confirm this result. Les protéines MAGE-A font partie d’une famille de protéines qui sont présentes dans de nombreux cancers humains de type histologique varié. Par contre, ces protéines sont absentes dans la plupart des tissus sains, à l’exception du testicule et du placenta.
Les fonctions des protéines MAGE-A étant peu connues, l’objectif de mon mémoire était de la caractériser dans les cellules de trophoblastes humains qui ont la particularité d’être invasives. L’implantation du fœtus réalisée par le trophoblaste dans l’endomètre maternel présente des ressemblances avec les propriétés invasives des cellules cancéreuses. L’inhibition de l’expression constitutive des protéines MAGE-A dans des cellules de placenta pourrait permettre de déterminer si leur rôle est d’influencer la migration et l’invasivité de ces cellules. Par la suite, on pourrait évaluer si les protéines MAGE-A sont impliquées dans la prolifération et les propriétés métastasiques des cellules tumorales.
En premier lieu, il était essential de commencer par caractériser l’expression des gènes MAGE-A dans les trophoblastes du premier trimestre par PCR qualitative, afin d’identifier les gènes de cette famille qui devaient être ciblés spécifiquement. Les résultats obtenus concordent avec ceux des études précédentes et montrent que le gène MAGE-A10 est le plus fréquemment et le plus fortement exprimé dans des cultures primaires de cellules trophoblastiques précoces. Par contre, des lignées de choriocarcinome dérivées de tumeurs trophoblastiques ont un profil d’expression des MAGE-A différents de celui des trophoblastes sains provenant de cultures primaires de placenta. Le profil d’expression des MAGE dans ces tumeurs se rapproche plus de celui qui est observé dans d’autres types de tumeurs, tels que les mélanomes.
En second lieu, un pool d’ARN interférents ciblant spécifiquement le transcript MAGE-A10 a été testé dans une lignée de mélanome LB373-MEL exprimant fortement MAGE-A10. L’ARN interférent le plus efficace a été mis en évidence par des techniques de PCR quantitative et de Western Blot. Des cultures primaires de trophoblastes humains précoces on été transfectées avec cet ARN interférent. Les résultats des PCR quantitative et des Western Blot ont montré une diminution du niveau d’expression du transcrit MAGE-A10 au maximum d’un facteur 5 maximum en présence de l’ARN interférent. Ces cellules trophoblastiques modifiées ont été soumises à des tests de migration et d’invasion afin d’étudier les conséquences de cette inhibition. Nous n’avons pas mis en évidence de migration de trophoblastes traités ou non traités. Les tests d’invasion ont démontré qu’il y avait une diminution d’un facteur 3 des capacités invasives des cellules traitées avec un ARN interférent anti-MAGE-A1 ou avec l’ARN interférent ciblant MAGE-A10 par rapport aux cellules trophoblastiques non traitées. Le même résultat a été obtenu pour la lignée de mélanome ME248.3 exprimant majoritairement MAGE-A10.
La protéine MAGE-A10 pourrait donc être impliquée dans l’invasion des cellules trophoblastiques et des cellules tumorales. Mais les expériences doivent être reproduites pour confirmer ces résultats

MAGE-A10 antigen --- melanoma-specific antigens --- Trophoblasts --- Neoplasm Proteins

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The placenta is an organ that connects the developing fetus to the uterine wall, thereby allowing nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. Proper vascular development in the placenta is fundamental to ensuring a healthy fetus and successful pregnancy. This book provides an up-to-date summary and synthesis of knowledge regarding placental vascular biology and discusses the relevance of this vascular bed to the functions of the human placenta.

Fetal stem cells -- Physiology. --- Placental circulation -- Physiology. --- Trophoblasts -- Physiology. --- Blastocyst --- Stem Cells --- Placenta --- Receptor Protein-Tyrosine Kinases --- Blood Circulation --- Endocrine Cells --- Receptors, Growth Factor --- Embryonic Structures --- Protein-Tyrosine Kinases --- Cells --- Embryo, Mammalian --- Receptors, Cell Surface --- Receptors, Peptide --- Cardiovascular Physiological Processes --- Anatomy --- Membrane Proteins --- Protein Kinases --- Cardiovascular Physiological Phenomena --- Proteins --- Circulatory and Respiratory Physiological Phenomena --- Phosphotransferases (Alcohol Group Acceptor) --- Fetal Stem Cells --- Trophoblasts --- Receptors, Vascular Endothelial Growth Factor --- Placental Circulation --- Phosphotransferases --- Amino Acids, Peptides, and Proteins --- Phenomena and Processes --- Transferases --- Chemicals and Drugs --- Enzymes --- Enzymes and Coenzymes --- Human Anatomy & Physiology --- Zoology --- Health & Biological Sciences --- Physiology --- Animal Anatomy & Embryology --- Blood-vessels. --- blood supply. --- placenta circulation --- trophoblast --- angiogenesis --- vasoactivity --- placental stem cells

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HIV Infections --- Placenta --- Pregnancy Complications, Infectious --- Trophoblasts --- transmission. --- microbiology. --- therapy. --- immunology. --- Communicable diseases in pregnancy --- Communicable diseases in the fetus --- Trophoblast --- Congresses. --- Cytochemistry --- Immunology --- Infections --- immunology --- congresses. --- congenital --- therapy --- Hiv infections --- Pregnancy complications, infectious --- Congenital --- Therapy --- Blastocyst --- Cotyledon (Anatomy) --- Embryology --- Uterus, Pregnant --- Fetus --- Pregnancy --- Congresses --- Cytochemistry&delete& --- Immunology&delete& --- Infections&delete& --- transmission --- microbiology --- Diseases --- Complications

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Despite significant progress in molecular epigenetic research and its enormous potential, there are still considerable challenges to overcome before we can fully understand the role of epigenetic processes in brain function and behavior. For instance, what comprises a ‘normal’ brain epigenome and what is the degree of region- and cellular-specificity of epigenetic landscapes in the brain? How do the multiple layers of epigenetic information interact and change over time? How common is meiotic epigenetic heritability and what role it may play in complex psychiatric disease? To what extent is the epigenome plastic and malleable in response to environmental influences? This volume demonstrates that such questions can now be explored in an experimental molecular biology laboratory. While the community is only just starting to acknowledge the importance of epigenetic processes in the brain, there is no doubt that numerous breakthrough discoveries in brain and behavioral epigenetics will be made in the decades to come.

Behavior genetics. --- Brain -- Diseases -- Genetic aspects. --- Brain -- Genetic aspects. --- Epigenesis. --- Genetic polymorphisms. --- Genetics. --- Neurogenetics. --- Pharmacogenetics. --- Trophoblasts. --- Epigenesis --- Genetic regulation --- Brain --- Genomics --- Environmental Pollution --- Central Nervous System --- Behavior and Behavior Mechanisms --- Psychiatry and Psychology --- Computational Biology --- Nervous System --- Public Health --- Genetics --- Environment and Public Health --- Biology --- Anatomy --- Biological Science Disciplines --- Health Care --- Natural Science Disciplines --- Disciplines and Occupations --- Epigenomics --- Behavior --- Mental Disorders --- Environmental Exposure --- Medicine --- Health & Biological Sciences --- Pathology --- Behavior genetics --- Behavior genetic analysis --- Behavioral genetics --- Human behavior genetics --- Psychogenetics --- Medicine. --- Human genetics. --- Psychiatry. --- Biomedicine. --- Human Genetics. --- Embryology --- Evolution (Biology) --- Psychology --- Medicine and psychology --- Mental health --- Psychology, Pathological --- Heredity, Human --- Human biology --- Physical anthropology