Molecular and metabolic retinoid pathways in human amniotic membranes

Vitamin A (retinol) and its active derivatives (the retinoids) are essential for the growth and development of the mammalian fetus and placenta. The amniotic membranes are extra-embryonic structures that are indispensable for normal gestation in mammals. Although placental involvement of retinoids is clearly established, little is known about the roles of retinoids for the associated amniotic membranes. The aim of this study was to define the metabolic and molecular pathways of retinoic signaling in human fetal membranes. The expression of retinoid receptors (RARalpha, beta and RXRalpha, beta) was established at transcript and protein levels. Enzymes involved in retinoic acid generation were also detected. The enzymatic generation of functional retinoids was confirmed using specific inhibitors of retinol metabolism. Finally, the functionality of retinoid pathways was demonstrated by inducing established retinoid target gene expression. Our results clearly demonstrated that the molecular and metabolic actors of retinoic signaling pathways are functional in human fetal membranes.