Thromboxane A2 limits differentiation and enhances apoptosis of cultured human trophoblasts

Kamran Yusuf, Steve D. Smith, Roni Levy, W. Timothy Schaiff, Solange M. Wyatt, Yoel Sadovsky, D. Michael Nelson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Prostanoids influence differentiation in diverse cell types. Altered expression of cyclooxygenase and prostaglandins has been implicated in the pathophysiology of placental dysfunction, which results in preeclampsia and fetal growth restriction. We hypothesized that prostanoids modulate differentiation and apoptosis in cultured human trophoblasts. Villous cytotrophoblasts were isolated from term human placentas and cultured in serum-free medium. The level of human chorionic gonadotropin was used as a marker of biochemical differentiation of primary trophoblasts, and syncytia formation was used as a marker of morphologic differentiation. Of the prostanoids tested, we found exposure to thromboxane A2 hindered both biochemical and morphologic differentiation of cultured trophoblasts. As expected, human chorionic gonadotropin levels in the media were elevated in a concentration-dependent manner in the presence of the thromboxane synthase inhibitor, sodium furegrelate, or the thromboxane A2 receptor blocker SQ 29,548. Furthermore, thromboxane A2 enhanced trophoblast apoptosis, determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, cell morphology, and a concentration-dependent increase in p53 expression. We conclude that thromboxane A2 hinders differentiation and enhances apoptosis in cultured trophoblasts from term human placenta. We speculate that thromboxane may contribute to placental dysfunction by restricting differentiation and enhancing apoptosis in human trophoblasts.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalPediatric Research
Volume50
Issue number2
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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