Developmental Changes in Endogenous Retinoids during Pregnancy and Embryogenesis in the Mouse1

Satre, Michael; Ugen, K E; Kochhar, D. M.

doi:10.1095/biolreprod46.5.802

Cited by 52 publications

(44 citation statements)

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“…This hypothesis is supported by results concerning the switch in retinoid content of embryonic and placental compartments during the development of the mouse conceptus (9). During early organogenesis, the retinyl ester content of the placenta is nearly 8-fold higher than the content of the embryo, whereas at the end of gestation, the retinyl ester content of embryo is nearly 4-fold greater than that of the placenta.…”

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confidence: 62%

“…Because there is no de novo fetal synthesis of retinol, the developing mammalian embryo is dependent on the maternal circulation for its vitamin A intake. The presence of measurable hepatic vitamin A stored at birth is indicative of the functionality and importance of placental transport during pregnancy (9,10). Abnormalities of placental transfer could have serious consequences on fetal development and integrity.…”

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confidence: 99%

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Esterification of Vitamin A by the Human Placenta Involves Villous Mesenchymal Fibroblasts

et al. 2000

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Vitamin A (retinol) and its active derivatives (retinoic acids) are essential for growth and development of the mammalian fetus. Maternally derived retinol must pass the placenta to reach the developing fetus. Despite its apparent importance, little is known concerning placental transfer and metabolism of retinol, and particularly of placental production and storage of retinyl esters. To elucidate this metabolic pathway, we incubated, in the presence of retinol, 1) human full-term placental explants and 2) primary cultures of major cells types contributing to placental function: trophoblasts and villous mesenchymal fibroblasts. We used HPLC to determine the types and concentrations of retinyl esters produced by these explants and cells. About 14% of total cellular retinol in placental explants was esterified. The most abundant esters were myristate and palmitate. Primary cell cultures showed that fibroblasts efficiently produced retinyl esters, but trophoblasts did not. In both types of experiments, no retinyl esters were detected in the culture medium, suggesting that retinyl esters were produced for storage purpose. These results suggest that villous mesenchymal fibroblasts are primary sites of retinol esterification and storage in the placenta. In addition to their essential roles in vision, growth, and maintenance of differentiated epithelia, vitamin A (retinol) and its active derivatives, the RAs, are required for normal mammalian reproduction and fetal development (1, 2). Maternal vitamin A deficiency can result in fetal death or in a spectrum of malformations, the fetal vitamin A deficiency syndrome (3-6). Excessive vitamin A intake can also produce a spectrum of congenital defects, in a dose-and developmental stagedependent manner (7,8). Because there is no de novo fetal synthesis of retinol, the developing mammalian embryo is dependent on the maternal circulation for its vitamin A intake. The presence of measurable hepatic vitamin A stored at birth is indicative of the functionality and importance of placental transport during pregnancy (9, 10). Abnormalities of placental transfer could have serious consequences on fetal development and integrity.Despite its apparent importance, little is known about placental transfer and metabolism of retinoids. This question has been approached in animal models (sheep, mouse, monkey), but the placental metabolism of retinoids is difficult to deduce from studies in the intact animal, and extrapolation of these results to humans is uncertain (11-13). Measurements of human placental, maternal, and cord retinoid concentrations have been reported, but they shed little light on the metabolic pathway (14,15). Experiments using human perfused placenta and full-term human placental tissues in vitro have yielded controversial results concerning retinoid metabolism, especially the ability of the placenta to produce and store retinyl esters from retinol (16,17).To better characterize retinoid metabolism, we have investigated placental capacity to esterify retinol into retinyl es...

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confidence: 62%

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confidence: 99%

Esterification of Vitamin A by the Human Placenta Involves Villous Mesenchymal Fibroblasts

et al. 2000

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“…RA is normally present in mouse serum at 4 ng/ml (37). Treatment of wild-type mice with retinol resulted in a peak RA concentration of 1170 ng/ml (Fig.…”

Section: Ra Synthesis During Acute Ethanol Treatment Of Wild-typementioning

confidence: 92%

Retinol/Ethanol Drug Interaction during Acute Alcohol Intoxication in Mice Involves Inhibition of Retinol Metabolism to Retinoic Acid by Alcohol Dehydrogenase

Molotkov

Duester

2002

Journal of Biological Chemistry

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Substantial evidence indicates that one consequence of alcohol intoxication is a reduction in retinoic acid (RA) levels. Studies on the mechanism have shown that chronic ethanol consumption induces P450 enzymes that increase RA degradation, thus accounting for much but not all of the observed decrease in RA. A reduction in RA synthesis may also be involved as ethanol competitively inhibits retinol oxidation catalyzed by alcohol dehydrogenase (ADH) in vitro. This may be important during acute ethanol intoxication and may contribute to adverse retinol/ethanol drug interactions. Here we have examined mice for the effect of either acute ethanol intoxication or Adh1 gene disruption on RA synthesis and degradation. RA produced following a dose of retinol (50 mg/kg) was reduced 87% by pretreatment with an intoxicating dose of ethanol (3.5 g/kg). RA produced in Adh1-null mutant mice following a 50-mg/kg dose of retinol was reduced 82% relative to wild-type mice, thus similar to wild-type mice pretreated with ethanol. Reduced RA production was associated with increased retinol levels in both ethanol-treated wild-type mice and Adh1-null mutant mice, indicating reduced clearance of the retinol dose. RA degradation following a dose of RA (10 mg/kg) was increased only 42% by ethanol pretreatment (3.5 g/kg) and only 26% in Adh1-null mutant mice relative to wild-type mice. These findings demonstrate that the reduced RA levels observed during acute retinol/ethanol drug interaction are due primarily to a decrease in ADH-catalyzed RA synthesis and secondarily to an increase in RA degradation.

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“…Excess retinoic acid may also disrupt events associated with Sertoli cell mesenchymal to epithelial cell transition that occurs early in testis development. Retinoic acid is required for normal morphogenesis of the embryo and cannot be synthesized de novo (32). However, detrimental effects have been observed when retinoic acid is present at concentrations higher than optimal levels (33).…”

Section: Discussionmentioning

confidence: 99%

Action of Retinoids on Embryonic and Early Postnatal Testis Development

et al. 1999

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Developmental Changes in Endogenous Retinoids during Pregnancy and Embryogenesis in the Mouse1

Cited by 52 publications

References 0 publications

Esterification of Vitamin A by the Human Placenta Involves Villous Mesenchymal Fibroblasts

Esterification of Vitamin A by the Human Placenta Involves Villous Mesenchymal Fibroblasts

Retinol/Ethanol Drug Interaction during Acute Alcohol Intoxication in Mice Involves Inhibition of Retinol Metabolism to Retinoic Acid by Alcohol Dehydrogenase

Action of Retinoids on Embryonic and Early Postnatal Testis Development

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