Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate

Junli Yan, Satoshi Tanaka, Mayumi Oda, Tsunehisa Makino, Jun Ohgane, Kunio Shiota*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)


Trophoblast stem cell (TS cell) lines have the ability to differentiate into trophoblast subtypes in vitro and contribute to the formation of placenta in chimeras. In order to investigate the possible role of retinoic acid (RA) in placentation, we analyzed the effects of exogenous RA on TS cells in vitro and the developing ectoplacental cone in vivo. TS cells expressed all subtypes of the retinoid receptor family, with the exception of RARβ, whose expression was stimulated in response to RA. TS cells treated with RA were compromised in their ability to proliferate and exhibited properties of differentiation into trophoblast giant cells. During TS cell differentiation into trophoblast subtypes induced by withdrawal of FGF4, RA treatment further illustrated its role in the specification of cell fate by the promotion of differentiation into giant cells and the suppression of spongiotrophoblast formation. Moreover, administration of RA during pregnancy resulted in the overabundance of giant cells at the expense of spongiotrophoblast cells. RA hereby acts as an extracellular signal whose potential function can be linked to specification events mediating trophoblast cell fate. Taken together with the spatial patterns of giant-cell formation and RA synthesis in vivo, these findings implicate a function for RA in giant-cell formation during placentation.

Original languageEnglish
Pages (from-to)422-432
Number of pages11
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 2001 Jul 15
Externally publishedYes


  • Cell fate
  • Ectoplacental cone
  • Retinoic acid
  • Spongiotrophoblast cell
  • Trophoblast giant cell
  • Trophoblast stem cell (TS cell)

ASJC Scopus subject areas

  • Developmental Biology


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