Maternal–fetal transfer and metabolism of vitamin A and its precursor β-carotene in the developing tissues

Spiegler, Elizabeth; Kim, Youn‐Kyung; Wassef, Lesley; Shete, Varsha; Quadro, Loredana

doi:10.1016/j.bbalip.2011.05.003

Cited by 87 publications

(75 citation statements)

References 148 publications

(202 reference statements)

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“…That results in a high placental retinol level, which, through negative feedback, can decrease trophoblastic RARα and then RBP expression resulting in decreased pulmonary RBP and retinol level (19). In the circulation, retinol primarily exists in retinol-RBP formation, although at lower concentrations other forms of retinol circulate in the bloodstream such as RE incorporated in lipoprotein particles and RA (6). It has been demonstrated that nitrofen does not disturb the alternative, RBP-independent RE maternal-fetal retinol transport.…”

Section: Discussionmentioning

confidence: 99%

“…The placenta has a major role in retinol homeostasis in fetal life (5). As the fetus cannot synthesize retinol, it relies on circulating maternal retinol, which reaches the fetus by crossing the maternal-fetal barrier in the placenta (6). Although retinol-binding protein (RBP) is essential for retinol transport within the circulation (7), maternal RBP does not cross the placenta (8).…”

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confidence: 99%

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Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia

et al. 2015

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Background: Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH. Methods: Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. results: Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. conclusion: Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDHassociated PH by elevating serum and pulmonary retinol levels. t he mortality rate of infants born with congenital diaphragmatic hernia (CDH) remains high despite prenatal diagnosis and improved postnatal treatment strategies (1). The high morbidity and mortality is mainly attributed to pulmonary hypoplasia (PH) and associated persistent pulmonary hypertension (2). Much of the current understanding of the pathogenesis of PH in CDH originates from experimental animal studies. Maternal exposure to nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) in rodents during midgestation results in a high rate of CDH and associated PH in their fetuses, which is strikingly similar to the human condition (3).It is well understood that retinoids-vitamin A and its derivatives-are essential for the morphogenesis of most developing organs and tissues, including the lungs (4). The placenta has a major role in retinol homeostasis in fetal life (5). As the fetus cannot synthesize retinol, it relies on circulating maternal retinol, which reaches the fetus by crossing the maternal-fetal barrier in the placenta (6). Although retinol-binding protein (RBP) is essential for retinol transport within the circulation (7), maternal RBP does not cross the placenta (8). Therefore, in order to enter the fetal circulation, maternal retinol bound to maternal RBP must be released at the maternal-fetal interface. Fetal RBP is produced by the trophoblast and then forms a complex with retinol to be subsequently released into the fetal circulation and delivered to the ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia

et al. 2015

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“…In this context, it is important to note that RE from chylomicrons, the major transport mode of dietary vitamin A, can be transferred from the maternal circulation to the embryo (24). Additionally, existing evidence indicates that the maternal vitamin A status can imprint the size of secondary lymphoid organs and the efficiency of immune responses in the offspring (25).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor ISX mediates the cross talk between diet and immunity

Widjaja‐Adhi

Palczewski

Dale

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The intestinal epithelium is a major site for the conversion of dietary β-carotene to retinaldehyde by the enzyme BCO1. The majority of retinaldehyde is further metabolized to retinol (vitamin A), esterified and packaged into triacylglycerol-rich chylomicrons for bodily distribution. Some serve on-site for the synthesis of retinoic acid, a hormone-like compound, which exerts pleiotropic and dominant effects on gastrointestinal immunity. We report here that the intestine-specific homeobox protein ISX is critical to control the metabolic flow of β-carotene through this important branching point of vitamin A metabolism. This transcription factor represses Bco1 gene expression in response to retinoic acid signaling. In ISX-deficient mice, uncontrolled Bco1 gene expression led to increased retinoid production in the intestine. Systemically, this production resulted in highly elevated hepatic retinoid stores. In the intestine, it increased the expression of retinoic acid-inducible target genes such as Aldh1a2, Dhrs3, and Ccr9. The β-carotene-inducible disruption of retinoid homeostasis affected gut-homing and differentiation of lymphocytes and displayed morphologically in large lymphoid follicles along the intestine. Furthermore, it was associated with an infiltration of the pancreas by gut-derived lymphocytes that manifested as a pancreatic insulitis with β-islet cell destruction and systemic glucose intolerance. Thus, our study identifies an important molecular interlink between diet and immunity and indicates that vitamin A homeostasis must be tightly controlled by ISX to maintain immunity and tolerance at the intestinal barrier.carotenoids | retinoids | lymphocytes | intestine | BCO1

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“…9 In addition, LBW and very LBW prevalence is influenced by risk of disease and lack of prenatal care in some developing countries. 30 Healthy newborn infants from VA-sufficient mothers are already born with limited VA stores due to tight regulation of placental transfer, 4 thus it is not surprising that LBW infants born to mothers who are VA-deficient are compromised. Even in breastfed infants, preterm infants were found to have significantly lower plasma retinol concentrations than term infants at four weeks of age.…”

Section: Discussionmentioning

confidence: 99%

“…3 LBW infants are often underdeveloped physiologically and have minimal VA stores, because of highly regulated trans-placental transport. 4 Preterm infants need VA for proper lung and retina development. 5 Extremely LBW infants (defined as birth weight <1 kg) often have low plasma and tissue concentrations of VA. 6,7 Supplementation trials in LBW infants have yielded contraindicated results.…”

Section: Introductionmentioning

confidence: 99%

Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements

Heying

Hovel

Tanumihardjo

2015

Exp Biol Med (Maywood)

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A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n ¼ 18) and healthy birth weight (HBW) piglets (>1.5 kg, n ¼ 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 mmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n ¼ 3-5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 AE 0.09, 0.24 AE 0.10 mmol/g liver and 13.4 AE 4.1, 14.2 AE 4.5 nmol/g kidney, respectively) than controls (n ¼ 10) (0.051 AE 0.01 mmol/g liver and 1.01 AE 0.43 nmol/g kidney) (P ¼ 0.0061 and < 0.0001, respectively). Total liver (9.75 AE 5.16 mmol) and kidney retinol (204 AE 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P ¼ 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P ¼ 0.022, P ¼ 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 AE 4.4 mmol/L) than 25,000 IU (2.7 AE 2.3 mmol/L) (P ¼ 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth.

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Maternal–fetal transfer and metabolism of vitamin A and its precursor β-carotene in the developing tissues

Cited by 87 publications

References 148 publications

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia

Transcription factor ISX mediates the cross talk between diet and immunity

Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements

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