Trophoblast stem cell (TS cell) lines have the ability to differentiate int
o trophoblast subtypes in vitro and contribute to the formation of placenta
in chimeras. In order to investigate the possible role of retinoic acid (R
A) 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 RAR beta,
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 differentia
tion into trophoblast subtypes induced by withdrawal of FGF4, RA treatment
further illustrated its role in the specification of cell fate by the promo
tion of differentiation into giant cells and the suppression of spongiotrop
hoblast formation. Moreover, administration of RA during pregnancy resulted
in the overabundance of giant cells at the expense of spongiotrophoblast c
ells. RA hereby acts as an extracellular signal whose potential function ca
n 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 formatio
n during placentation. (C) 2001 Academic Press.