Transcriptional effects of hypoxia on fusiogenic syncytin and its receptor ASCT2 in human cytotrophoblast BeWo cells and in ex vivo perfused placental cotyledons

Am J Obstet Gynecol. 2003 Aug;189(2):583-8. doi: 10.1067/s0002-9378(03)00538-6.

Abstract

Objective: The purpose of this study was to test the hypothesis that hypoxia down-regulates placental syncytin, which could play a role in altered placentogenesis; we investigated the influence of hypoxia on syncytin and its receptor ASCT2 gene expression in BeWo cells and in ex vivo perfused human cotyledons.

Study design: BeWo cells were incubated with deferoxamine or cobalt chloride under normoxia and hypoxia. Additionally, a model of dually ex vivo perfused cotyledons was applied. Under hypoxic and cobalt chloride stimuli syncytin, ASCT2, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, and beta(2)-microglobulin (beta(2)-MG) messenger RNAs were analyzed with the use of real-time polymerase chain reaction.

Results: Hypoxia, deferoxamine, and cobalt chloride markedly decreased syncytin messenger RNA in BeWo cells, whereas ASCT2 messenger RNA was not altered significantly. In isolated perfused cotyledons, hypoxia also reduced syncytin (P<.05) but not ASCT2 messenger RNA.

Conclusion: Our data provide first evidence that syncytin gene expression is down-regulated by hypoxia, which strengthens the hypothesis that syncytin is reduced in disturbed pregnancies in the course of placental hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System ASC / genetics*
  • Cell Line
  • Cobalt / pharmacology
  • Computer Systems
  • Deferoxamine / pharmacology
  • Down-Regulation
  • Female
  • Gene Products, env / genetics*
  • Gene Products, env / metabolism
  • Humans
  • Hypoxia / genetics*
  • In Vitro Techniques
  • Iron Chelating Agents / pharmacology
  • Minor Histocompatibility Antigens
  • Placenta / metabolism*
  • Polymerase Chain Reaction
  • Pregnancy
  • Pregnancy Proteins / genetics*
  • Pregnancy Proteins / metabolism
  • RNA, Messenger / metabolism
  • Transcription, Genetic*
  • Trophoblasts / metabolism*

Substances

  • Amino Acid Transport System ASC
  • Gene Products, env
  • Iron Chelating Agents
  • Minor Histocompatibility Antigens
  • Pregnancy Proteins
  • RNA, Messenger
  • SLC1A5 protein, human
  • syncytin
  • Cobalt
  • cobaltous chloride
  • Deferoxamine