A retinoic acid receptor α antagonist counteracts retinoid teratogenicity in vitro and reduced incidence and/or severity of malformations in vivo

Abstract

The role of retinoic acid receptors (RAR) in retinoid-induced teratogenesis is mainly unknown. The aim of the present studies was to demonstrate the effect of a RARα antagonist on retinoid-induced teratogenic effects in vitro and in vivo. In micromass cultures of rat limb bud cells a RARα antagonist was able to counteract differentiation inhibiting effects of a RARα agonist. In mouse studies, the selective RARα antagonist reduced frequency and/or severity of major malformations. Our observations indicate the potentiality of selective RAR agonists and antagonists in dissecting the function of nuclear receptors and in particular cases of retinoid teratogenesis, to assign to the different receptors a primary role in determining one or another of the multiple malformations.