Molecular Biology of Human Placental Development

GENTI DE RAIMONDI SUSANA

Buenos Aires

Congreso; Sociedad Argentina de Biología; 2010

MOLECULAR BIOLOGY OF HUMAN PLACENTAL DEVELOPMENT Genti-Raimondi S. CIBICI-CONICET, Dpto. de Bioqca Clínica, Facultad de Ciencias Químicas, UNC, Córdoba. Argentina. E-mail: sgenti@fcq.unc.edu.ar Placental cytotrophoblasts (CTBs) proliferate and differentiate, by fusion, to form a syncytiotrophoblast (STB), event that starts with modifications of the plasma membranes of both partners such as expression of syncytin, connexin 43 and enrichment of phosphatidylserine on the STB surface. We have reported the cloning and characterization of a new member of the START family, involved in the intracellular lipid transport, up-regulated in the choriocarcinoma JEG-3 cell line, denominated StarD7. Elisa assays revealed that StarD7 binds cardiolipin, phosphatidylserine and phosphatidylcholine. In addition, an increased StarD7 protein expression and subcellular relocalization were observed in in vitro differentiating cytotrophoblast. Furthermore, we have shown that β-catenin activates human StarD7 expression. By other side, StarD7 silencing led to a marked decrease of Twist1, Cnx43, MBD2, ABCG2 and TGFβRII mRNA levels. In contrast, knocking down StarD7 increased the expression of syncytial formation markers, such as b-hCG protein production and secretion, β-hCG mRNA levels, as well as GCM1, a transcriptional factor required for syncitialization. In addition, a reduction of intercellular desmosomes between adjacent JEG-3 cells after ablation of StarD7 expression was observed, suggesting that StarD7 play a key role in the gene expression control relevant to normal development of trophoblast differentiation. Supported by MinCyT of Córdoba, CONICET, FONCyT and SECyT-UNC