title: Oxygen tension directs the differentiation pathway of human cytotrophoblast cells.
abstract: During placental development, human cytotrophoblast cells can differentiate to either villous syncytiotrophoblast cells or invasive extravillous trophoblast cells. We hypothesize that oxygen tension plays a critical role in determining the pathway of cytotrophoblast differentiation. A highly purified preparation of cytotrophoblast cells from human third trimester placenta was cultured for 5 days in either 20% or 1% oxygen tension. The cells incubated at 20% oxygen formed a syncytium as determined by immunohistochemistry using an anti-desmosomal protein antibody that identifies cell membranes. In addition, the mRNA was markedly induced for syncytin, a glycoprotein shown to be essential for syncytiotrophoblast formation, and for human placental lactogen (hPL), which is a specific marker for syncytiotrophoblast cells. In contrast, the cell incubated at 1% oxygen tension did not fuse by morphologic analysis and did not express syncytin or hPL mRNA. However, these cells expressed abundant amounts of HLA-G, a specific marker for extravillous trophoblast cells, which was not seen in cells incubated at 20% oxygen tension. These results suggest that low oxygen tension directs differentiation along the extravillous trophoblast cell pathway while greater oxygen tension directs differentiation along the villous trophoblast cell pathway.
authors: Department of Obstetrics and Gynecology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. jared.robins@brown.edu
authors: J C
authors: JC
authors: Robins
authors: A
authors: A
authors: Heizer
authors: A
authors: A
authors: Hardiman
authors: M
authors: M
authors: Hubert
authors: S
authors: S
authors: Handwerger
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015726:Giant Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D010929:Placentation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D010100:Oxygen