In human diet, beta-carotene is the principal source of vitamin A, which is essential for normal embryonic development. Beta-carotene supplementation in pregnant women has proven to be effective to counteract the detrimental effects of vitamin A deficiency. Our lab has unequivocally shown that, in mice, intact beta-carotene supplemented during pregnancy can cross the placenta and can be efficiently metabolized by the embryo to generate retinoids. However, the mechanisms by which beta-carotene is acquired by the developing tissues from the maternal blood and key regulators involved in such uptake are unknown. Furthermore, whether maternal dietary vitamin A intake and status influence the uptake of this carotenoid by the developing tissues has never been investigated. Our study aimed at addressing these issues by investigating whether and how maternal vitamin A status and dietary intake affect uptake of beta-carotene by the developing tissues. Furthermore, since LDL-receptor internalizes majority of beta-carotene carrying lipoproteins, we investigated whether this receptor mediates beta-carotene uptake by maternal as well as the developing tissues. We showed that marginal vitamin A deficient status of mothers, in the case of mice lacking the retinol esterification enzyme (LRAT) and retinol-binding protein (RBP), led to an increased beta-carotene uptake in the placenta. It also led to an altered metabolism of beta-carotene in the developing tissues. Furthermore, we demonstrated that upon beta-carotene supplementation of wild-type dams, placental transcription of chylomicron-remnant receptor LRP1 and VLDL-receptor were donwregulated. We also showed that maternal excessive dietary vitamin A intake resulted in negligible accumulation of beta-carotene in embryos. Our data indicate that the regulation of placental lipoprotein assembly and secretion could control embryonic acquisition of beta-carotene. We demonstrated that LDL-receptor (LDLr) may partially mediate the beta-carotene uptake in maternal liver. Under the conditions of higher serum lipoprotein accumulation, in the case of mice lacking LDLr, it may facilitate placental beta-carotene uptake. Our preliminary data suggested that regulation of placental lipoprotein assembly and secretion may control the transfer of beta-carotene to the embryo in absence of both maternal and placental LDLr. Overall, these findings expanded our knowledge of mechanisms and key regulators of beta-carotene uptake in the developing tissues.
Subject (authority = RUETD)
Topic
Food Science
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_1746
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiii, 175 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Varsha V. Shete
Subject (authority = ETD-LCSH)
Topic
Lipoproteins--Receptors
Subject (authority = ETD-LCSH)
Topic
Beta carotene
Subject (authority = ETD-LCSH)
Topic
Vitamin A deficiency
Subject (authority = ETD-LCSH)
Topic
Pregnancy--Nutritional aspects
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
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