Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta

D. Michael Nelson, Roger D. Johnson, Steven D. Smith, Eyal Y. Anteby, Yoel Sadovsky

    Research output: Contribution to journalArticlepeer-review

    116 Scopus citations

    Abstract

    OBJECTIVE: We determined the effect of hypoxic conditions on cellular differentiation and prostaglandin H synthase expression in cultured human term trophoblast. STUDY DESIGN: Cytotrophoblasts isolated from term placentas were cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmosphere. Trophoblast biochemical differentiation was determined by release of human chorionic gonadotropin. Morphologic differentiation was evaluated by epifluorescent and confocal microscopic examination of cultures after dual cytochemical staining for surface membrane desmosomes and intracytoplasmic nuclei. Prostaglandin H synthase 2 expression was determined by Western blot analysis and correlated with enzyme activity by immunoassay of 2 prostaglandin H synthase 2 products, prostaglandin E2 and thromboxane. RESULTS: Human chorionic gonadotropin levels in media and syncytiotrophoblast formation were markedly diminished in trophoblast cultured in hypoxia, compared with trophoblast in control cultures, whereas viability was unchanged. Hypoxia up-regulated expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H synthase 1 and increased prostaglandin E2 and thromboxane release. CONCLUSIONS: Hypoxia limits differentiation and enhances prostaglandin H synthase 2 expression in cultured villous trophoblast. These responses may account for the cytotrophoblast prominence characteristic of placentas exposed to attenuated oxygen delivery.

    Original languageEnglish
    Pages (from-to)896-902
    Number of pages7
    JournalAmerican Journal of Obstetrics and Gynecology
    Volume180
    Issue number4
    DOIs
    StatePublished - 1 Jan 1999

    Keywords

    • Differentiation
    • Hypoxia
    • Placenta
    • Prostaglandin H synthase 2
    • Trophoblast

    ASJC Scopus subject areas

    • Obstetrics and Gynecology

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