The nutritional status of the mother is a key factor for the development and growth of the fetus. Vitamin A is an essential nutrient for the developing embryo, which depends on maternal circulating vitamin A (or retinoids) to fulfill its needs. Indeed, embryonic vitamin A-deficiency as well as -excess result in fetal malformations, representing a serious problem in both the developing world and the industrialized countries. Humans rely mainly on provitamin A carotenoids as a source of vitamin A. ?-carotene is the best-characterized vitamin A precursor and the most abundant supply of this nutrient in the human diet. Two enzymes, ?-carotene-15, 15'-oxygenase (CMO I) and ?-carotene-9, 10'-oxygenase (CMO II), have been identified as catalysts for the cleavage of specific double bonds of ?-carotene, resulting in the formation of vitamin A. At present, the role of ?-carotene in maternal-fetal nutrition is not well understood. Evidences from the literature suggest that this carotenoid may be an important, localized source of vitamin A for the developing tissues. We plan to address this crucial biological question by using mice lacking both CMO I and retinol-binding protein (RBP), the sole specific carrier for retinol in the circulation. We will also use mice lacking low density lipoprotein receptor (LDLr) or class B scavenger receptor (SR-BI) or lipoprotein lipase (LPL) to investigate the role of these key players of the lipid metabolism in facilitating the maternal-fetal transfer of ?-carotene.
Three specific aims are proposed: (1) To identify factors that modulate the expression of CMO I and CMO II during mouse development. (2) To determine whether ?-carotene is an alternative source of vitamin A for embryonic synthesis of retinoids. (3) To investigate the mechanisms of uptake and processing of ?-carotene by the maternal-fetal barrier (i.e., placenta and yolk sac). These studies will ultimately expand our knowledge of maternal-fetal nutrition and dietary contribution to embryonic development, thus providing new insight into appropriate dietary practices during pregnancy. These studies have a significant impact on human health, since they aim at reducing the incidence of fetal malformations associated with an abnormal maternal intake of micronutrients, such as vitamins.
|Marquez, Hector A; Cardoso, Wellington V (2016) Vitamin A-retinoid signaling in pulmonary development and disease. Mol Cell Pediatr 3:28|
|Shabrova, Elena; Hoyos, Beatrice; Vinogradov, Valerie et al. (2016) Retinol as a cofactor for PKC?-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. FASEB J 30:1339-55|
|Shete, Varsha; Costabile, Brianna K; Kim, Youn-Kyung et al. (2016) Low-Density Lipoprotein Receptor Contributes to ?-Carotene Uptake in the Maternal Liver. Nutrients 8:|
|Costabile, Brianna K; Kim, Youn-Kyung; Iqbal, Jahangir et al. (2016) ?-Apo-10'-carotenoids Modulate Placental Microsomal Triglyceride Transfer Protein Expression and Function to Optimize Transport of Intact ?-Carotene to the Embryo. J Biol Chem 291:18525-35|
|Kim, Youn-Kyung; Zuccaro, Michael V; Costabile, Brianna K et al. (2015) Tissue- and sex-specific effects of ?-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice. Arch Biochem Biophys 572:11-8|
|Wassef, Lesley; Shete, Varsha; Costabile, Brianna et al. (2015) High Preformed Vitamin A Intake during Pregnancy Prevents Embryonic Accumulation of Intact ?-Carotene from the Maternal Circulation in Mice. J Nutr 145:1408-14|
|Chen, Felicia; Marquez, Hector; Kim, Youn-Kyung et al. (2014) Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J Clin Invest 124:801-11|
|Dixon, Joseph L; Kim, Youn-Kyung; Brinker, Anita et al. (2014) Loss of ?-carotene 15,15'-oxygenase in developing mouse tissues alters esterification of retinol, cholesterol and diacylglycerols. Biochim Biophys Acta 1841:34-43|
|Wassef, L; Spiegler, E; Quadro, L (2013) Embryonic phenotype, *-carotene and retinoid metabolism upon maternal supplementation of *-carotene in a mouse model of severe vitamin A deficiency. Arch Biochem Biophys 539:223-9|
|Shete, Varsha; Quadro, Loredana (2013) Mammalian metabolism of ?-carotene: gaps in knowledge. Nutrients 5:4849-68|
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