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

OBJECTIVE: We determined the effect of hypoxic conditions on cellular diffe rentiation and prostaglandin H synthase expression in cultured human term t rophoblast. STUDY DESIGN: Cytotrophoblasts isolated from term placentas were cultured f or 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmo sphere. Trophoblast biochemical differentiation was determined by release o f human chorionic gonadotropin. Morphologic differentiation was evaluated b y epifluorescent and confocal microscopic examination of cultures after dua l cytochemical staining for surface membrane desmosomes and intracytoplasmi c nuclei. Prostaglandin H synthase 2 expression was determined by Western b lot analysis and correlated with enzyme activity by immunoassay of 2 prosta glandin H synthase 2 products, prostaglandin E-2 and thromboxane. RESULTS: Human chorionic gonadotropin levels in media and syncytiotrophobla st formation were markedly diminished in trophoblast cultured in hypoxia, c ompared with trophoblast in control cultures, whereas viability was unchang ed. Hypoxia up-regulated expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H synthase I and increased prostaglandin E-2 an d thromboxane release. CONCLUSIONS: Hypoxia limits differentiation and enhances prostaglandin H sy nthase 2 expression in cultured villous trophoblast. These responses may ac count for the cytotrophoblast prominence characteristic of placentas expose d to attenuated oxygen delivery.