Vitamin A and beta-carotene metabolism during mammalian embryonic development

The essential requirement of vitamin A for embryogenesis is well known. The mammalian embryo depends on maternal circulating retinoids (vitamin A and its metabolites) and pro-vitamin A carotenoids, mainly beta-carotene, for its supply of vitamin A. The mechanisms through which mammalian developing tissues maintain adequate retinoid levels in the face of suboptimal or excessive maternal dietary vitamin A intake have not been established. Also, whether and how the developing tissues metabolize beta-carotene as a "local" source of retinoids is not known.;To address these questions, this study investigated the role of retinyl ester formation catalyzed by lecithin:retinol acyltransferase (LRAT) in regulating retinoid homeostasis during embryogenesis. Also, this study examined the function of beta-carotene in maternal-fetal nutrition through the action of its cleavage enzyme, beta-carotene 15,15'-oxygenase (CMOI).;We revealed the existence of complex regulatory molecular mechanisms of retinoid homeostasis in embryonic tissues. We showed that, in the case of excessive maternal dietary vitamin A intake, LR acts together with Cyp26A1, one of the enzymes that catalyze the degradation of retinoic acid, and possibly with STRA6, the recently identified cell surface receptor for retinol-RBP, in maintaining adequate levels of retinoids in embryonic and extraembryonic tissues. The contribution of the pathway of retinoic acid synthesis to these regulatory processes becomes significant only under conditions of severe maternal vitamin A deficiency.;In addition, we demonstrated that intact beta-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoic acid (the active form of vitamin A) in the developing tissues by the action of CMOI. Maternally supplemented beta-carotene could be delivered to the embryos and the embryonic vitamin A deficiency (VAD) of embryo lacking both CMOI and RBP was improved. In the absence of beta-carotene in mouse diets, the observation that lack of CMOI in the RBP knockout developing tissues further exacerbates the severity of VAD was unexpected. Thus, we showed that CMOI exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of LRAT activity, at least in developing tissues.;These findings contributed to expand our knowledge of the molecular basis of maternal-fetal nutrition.