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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Integrative Nutrition and Metabolic Processes Study Section (INMP)
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Raiten, Daniel J
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Rutgers University
Schools of Earth Sciences/Natur
New Brunswick
United States
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