title: ERK1/2 and p38 regulate trophoblasts differentiation in human term placenta.
abstract: Mitogen-activated protein kinases (MAPKs) control many cellular events from complex programmes, such as embryogenesis, cell differentiation and proliferation, and cell death, to short-term changes required for homeostasis and acute hormonal responses. However, little is known about expression and activation of classical MAPKs, extracellular signal-regulated kinase1/2 (ERK1/2) and p38 in human placenta. Therefore, we examined the expression of ERK1/2 and p38 in trophoblasts from human term placenta, and their implication in differentiation. In vitro, freshly isolated cytotrophoblast cells, cultivated in 10% fetal bovine serum (FBS), spontaneously aggregate and fuse to form multinucleated cells that phenotypically resemble mature syncytiotrophoblasts, that concomitantly produce human chorionic gonadotropin (hCG) and human placental lactogen (hPL). This study shows that the level of ERK1/2 and p38 decreases with increasing days of culture, to reach an undetectable level after 5 days of culture. Moreover, pretreatment of cells with an ERK1/2-specific inhibitor (PD98059) and/or a p38-specific inhibitor (SB203580) suppressed trophoblast differentiation. Our results also demonstrate that the p38 pathway is highly solicited as compared to the ERK1/2 pathway in the differentiation process. Furthermore, ERK1/2 and p38 are rapidly activated upon addition of FBS, but the activation of p38 is delayed compared to that of ERK1/2. In summary, this study showed that ERK1/2 and p38 pathways are essential to mediate initiation of trophoblast differentiation.
authors.affiliation: Laboratoire de Physiologie materno-foetale, Départment des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada, H3C 3P8.
authors.forename: Georges
authors.initials: G
authors.lastname: Daoud
authors.forename: Marc
authors.initials: M
authors.lastname: Amyot
authors.forename: Eric
authors.initials: E
authors.lastname: Rassart
authors.forename: André
authors.initials: A
authors.lastname: Masse
authors.forename: Lucie
authors.initials: L
authors.lastname: Simoneau
authors.forename: Julie
authors.initials: J
authors.lastname: Lafond
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D006063:Chorionic Gonadotropin / Q000378:metabolism; D016895:Culture Media, Serum-Free; D003720:Densitometry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010920:Placenta / Q000166:cytology* / Q000201:enzymology*; D010928:Placental Lactogen / Q000378:metabolism; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000201:enzymology* / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D010928:Placental Lactogen; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048370:MAP Kinase Kinase 2; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one