Marceau Geoffroy, Gallot Denis, Borel Valérie, Lémery Didier, Dastugue Bernard, Dechelotte Pierre, Sapin Vincent
Université d'Auvergne, JE 2447, ARDEMO, F-63000 Clermont-Ferrand, France.
Biochem Biophys Res Commun. 2006 Aug 11;346(4):1207-16. doi: 10.1016/j.bbrc.2006.06.024. Epub 2006 Jun 12.
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.
维生素A（视黄醇）及其活性衍生物（类视黄醇）对于哺乳动物胎儿和胎盘的生长发育至关重要。羊膜是胚胎外结构，对哺乳动物的正常妊娠不可或缺。尽管类视黄醇在胎盘中的作用已明确确立，但关于类视黄醇对相关羊膜的作用却知之甚少。本研究的目的是确定人胎膜中视黄酸信号的代谢和分子途径。在转录和蛋白质水平确定了类视黄醇受体（RARα、β和RXRα、β）的表达。还检测了参与视黄酸生成的酶。使用视黄醇代谢的特异性抑制剂证实了功能性类视黄醇的酶促生成。最后，通过诱导已确立的类视黄醇靶基因表达证明了类视黄醇途径的功能。我们的结果清楚地表明，视黄酸信号通路的分子和代谢参与者在人胎膜中具有功能。
