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Trophoblast cell biology
France (ANEMF) - University of Versailles, Versailles
UPRES EA2293, laboratory of biology, Poissy Hospital
Prof P de Mazancourt
Prof P de Mazancourt
French and English only
Type of Research Project
- Basic science
What is the background of the project?
In human pregnancy, trophoblast cells play an essential role in embryo implantation and placental development. These cells can indeed differentiate according to one of two distinct pathways. In the extravillous pathway, cytotrophoblasts (CT) proliferate, differentiate into an invasive phenotype, and penetrate into the maternal decidua and myometrium. In the villous pathway, mononuclear CT fuse to form a specialized multinuclear syncytium called syncytiotrophoblast (ST), on the outer layer of placental villi. ST formation plays an important role in human placentation. This process can be affected in some pathological pregnancy situations. For example, altered ST formation was observed in human preeclampsia.
The ST layer is the site of many placental functions necessary for foetal growth and development, including nutrient, gas exchanges, and synthesis of steroid and peptide hormones. Characteristics related to trophoblast differentiation include the production of hormones like hCG, human placental lactogen and leptin. However, morphological changes, which involve fusion of CT to form the ST layer, represent a hallmark of this differentiation. Studies have highlighted the implication of adhesion molecules such as cadherins in trophoblast differentiation. Among these, E-cadherin is localized at the membrane of the isolated CT and disappears when the CT fuse into ST. Very recently, studies demonstrated the role of former envelope viral proteins derived from Human Endogenous Retrovirus (HERVs) in trophoblast cell fusion, of which syncytin-1 and syncytin-2 seem to be of high importance. Moreover, syncytin-2 mRNA and protein are particularly expressed in the ST.
Different in vitro studies have shown that the villous CT differentiation could be modulated by hormones and by soluble factors. For example, Epidermal Growth Factor (EGF), 17β-estradiol, Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), glucocorticoids, and hCG induce differentiation, whereas Tumor Necrosis Factor α (TNFα) and TGFβ1 impair this process. Adipokines like leptin and adiponectin have recently been shown to affect the reproductive system through central effects on the hypothalamus and/or peripheral effects on the ovary, endometrium, or directly on the embryo and placenta developments. Leptin is specifically expressed in the ST, and is considered as a new placental hormone. Adiponectin is a cytokine, predominantly produced by adipose tissue and present at high concentrations in human circulation. This adipokine is described as an insulin sensitising hormone, and has been shown to have anti-inflammatory, anti-angiogenic, anti-atherosclerotic, and anti-proliferative roles in various cell types. Adiponectin is a 30 kDa protein that is assembled into an array of complexes composed of multimers of adiponectin. The elaborate High Molecular Weight complex (HMW) is predominant in human circulation. Two specific adiponectin receptors, AdipoR1 and AdipoR2 have been identified. Both receptors contain seven transmembrane domains but are structurally and functionally distinct from G-protein coupled receptors. AdipoR1 and AdipoR2 are both expressed in human endometrium and placenta. However, adiponectin is only produced by endometrial cells at the foetal-maternal interface. An additional receptor for adiponectin, T-cadherin, has recently been described, but is not expressed in human trophoblast. AdipoR1 and AdipoR2 activate different signal transduction pathways. The AMPK pathway is known as the main signalling pathway activated by adiponectin. PKA, PI3K, and P38/P42/P44 MAPK pathways are also implicated in adiponectin effects. Recently, we have shown that adiponectin exerts anti-proliferative effects on trophoblastic cell lines (JEG-3 and BeWo) and also on human trophoblasts. However, to date, there are no data concerning the implication of adiponectin in trophoblast differentiation.
What is the aim of the project?
The aim of the project is to examine the proliferation and differenciation of throphoblasts cells and the interaction with some medicine.
What techniques and methods are used?
Observation of the differenciation of the throphoblast, marking, survival
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
The student will observe the practical experiments but will be highly involved in the analysis of the results, the tasks will be done by the tutor
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, some explanations and courses
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No premedical students
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
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