Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2589-2596 ◽  
Author(s):  
C. Chazaud ◽  
P. Chambon ◽  
P. Dolle
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Mouse Embryo ◽  
Time Course ◽  
Retinoic Acid Receptor ◽  
Mouse Embryos ◽  
Anteroposterior Patterning ◽  
Heart Looping ◽  
Left Right Asymmetry

Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.

scholarly journals A new approach to the assessment of marginal vitamin A deficiency in children in suburban Guwahati, India: hydrolysis of retinoyl glucuronide to retinoic acid

2008 ◽  
Vol 101 (6) ◽  
pp. 794-797 ◽  
Author(s):  
Pulin C. Sarma ◽  
Bhabesh C. Goswami ◽  
Krishna Gogoi ◽  
Harsha Bhattacharjee ◽  
Arun B. Barua
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Serum Retinol ◽  
Serum Samples ◽  
Group I ◽  
High Prevalence ◽  
Hydrolysis Of ◽  
Β Carotene

The objective of the present study was to determine marginal vitamin A deficiency (VAD) by testing the hydrolysis of retinoyl glucuronide (RAG) to retinoic acid (RA) in children. Previous studies in rats showed that hydrolysis occurred when rats were vitamin A deficient. Children (n 61) aged 3–18 years, were divided into two groups, I and II. Blood was collected from the children in Group I (n 19) who were not dosed with RAG. Children in Group II (n 42) were administered all-trans retinoyl glucuronide (RAG) orally, and blood was collected 4 h after the dose. All serum samples were analysed for retinoids and carotenoids. RA was detected in serum only when serum retinol was < 0·85 μmol/l. Thus, hydrolysis of RAG to RA occurred in children with VAD or marginal VAD. Serum retinol was < 0·35 μmol/l in twenty-one children, 0·35–0·7 μmol/l in twenty-three children, 0·7–0·9 μmol/l in eleven children and >1 μmol/l in six children. Mean serum retinol in sixty-one children was 0·522 (sd 0·315) μmol/l. Mean β-carotene (0·016 (sd 0·015) μmol/l) was far below normal compared to the level of lutein (0·176 (sd 0·10) μmol/l) in sixty-one children. A low β-carotene level might be due to a low intake of carotene but high demand for vitamin A. The RAG hydrolysis test may prove to be a useful approach for the determination of marginal VAD with no clinical or subclinical signs of VAD. High prevalence of VAD amongst certain communities in Assam cannot be ruled out.

scholarly journals Simultaneous Determination of all-trans-Retinoic Acid, β-Carotene, and Vitamin A in Galenic Preparations by Liquid Chromatography

2001 ◽  
Vol 84 (2) ◽  
pp. 354-360
Author(s):  
Vincenzo Pucci ◽  
Francesca Bugamelli ◽  
Roberto Mandrioli ◽  
Maria A Raggi
Keyword(s):  
Liquid Chromatography ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Degradation Products ◽  
Extraction Procedure ◽  
Uv Detector ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Β Carotene

Abstract The concentrations of vitamin A, β-carotene, and all-trans-retinoic acid in oral preparations were determined in a single analysis by a method based on isocratic, reversed-phase liquid chromatography (LC). The LC system consisted of a C18 column, a mobile phase of acetonitrile, dichloromethane, methanol, and water and a UV detector set at 330 nm. The linearity ranges were 25–250 ng/mL for trans-retinoic acid and vitamin A, and 100–1000 ng/mL for β-carotene. This LC method for the determination of retinoids is simple, precise, and accurate. No extraction procedure is required before the chromatographic analysis; only a suitable dilution is necessary. The method proved to be reliable, fast, and economical. Furthermore, this method is indicative of stability, because it allows for the determination of degradation products such as 13-cis-retinoic acid.

scholarly journals Effects of Vitamin-A Status on Hamster Tracheal Epithellum in Viva in Vitro

1989 ◽  
Vol 11 (3) ◽  
pp. 1-6 ◽  
Author(s):  
Luigi M. De Luca ◽  
Elizabeth M. McDowell
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Normal Liver ◽  
Acid Receptor ◽  
New Horizons ◽  
Vitamin A Status ◽  
Essential Nutrient ◽  
Hepatoma Tissue

In this paper we have suggested the new concept of exotrophic cells, i.e. cells that have conditionally escaped the need for an essential nutrient, such as vitamin A. These exotrophs might become fixed by a mutation and eventually contribute to the tumorigenic phenotype. The discovery of the retinoic acid receptor (RAR) has opened up new horizons in the search for the mechanism of action of retinoic acid [17; 18]. It is intriguing that a second retinoic acid receptor, RARE, is abundantly expressed in hepatoma tissue and not in normal liver; Benbrook et al. [191 suggest that the erroneous expression of the RARE might contribute to tumour development in liver. How and whether these findings relate to the vitamin-A-deficient status of hepatoma cells remains to be understood.

scholarly journals Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

1992 ◽  
Vol 286 (3) ◽  
pp. 755-760 ◽  
Author(s):  
S Kato ◽  
H Mano ◽  
T Kumazawa ◽  
Y Yoshizawa ◽  
R Kojima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Acid Receptor ◽  
Beta Gene

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2723-2748 ◽  
Author(s):  
D. Lohnes ◽  
M. Mark ◽  
C. Mendelsohn ◽  
P. Dolle ◽  
A. Dierich ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Congenital Malformations ◽  
Double Mutant ◽  
Congenital Abnormalities ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Acid Receptor ◽  
Null Mutants

Numerous congenital malformations have been observed in fetuses of vitamin A-deficient (VAD) dams [Wilson, J. G., Roth, C. B., Warkany, J., (1953), Am. J. Anat. 92, 189–217]. Previous studies of retinoic acid receptor (RAR) mutant mice have not revealed any of these malformations [Li, E., Sucov, H. M., Lee, K.-F., Evans, R. M., Jaenisch, R. (1993) Proc. Natl. Acad. Sci. USA 90, 1590–1594; Lohnes, D., Kastner, P., Dierich, A., Mark, M., LeMeur, M., Chambon, P. (1993) Cell 73, 643–658; Lufkin, T., Lohnes, D., Mark, M., Dierich, A., Gorry, P., Gaub, M. P., Lemeur, M., Chambon, P. (1993) Proc. Natl. Acad. Sci. USA 90, 7225–7229; Mendelsohn, C., Mark, M., Dolle, P., Dierich, A., Gaub, M.P., Krust, A., Lampron, C., Chambon, P. (1994a) Dev. Biol. in press], suggesting either that there is a considerable functional redundancy among members of the RAR family during ontogenesis or that the RARs are not essential transducers of the retinoid signal in vivo. In order to discriminate between these possibilities, we have generated a series of RAR compound null mutants. These RAR double mutants invariably died either in utero or shortly after birth and presented a number of congenital abnormalities, which are reported in this and in the accompanying study. We describe here multiple eye abnormalities which are found in various RAR double mutant fetuses and are similar to those previously seen in VAD fetuses. Interestingly, we found further abnormalities not previously reported in VAD fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ligand-Dependent Regulation of Retinoic Acid Receptor α in Rat Testis: In Vivo Response to Depletion and Repletion of Vitamin A

Endocrinology ◽  
1998 ◽  
Vol 139 (3) ◽  
pp. 1239-1248 ◽  
Author(s):  
Karin M. Akmal ◽  
Jannette M. Dufour ◽  
Mynuong Vo ◽  
Sarah Higginson ◽  
Kwan Hee Kim
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Acid Receptor ◽  
Rat Testis ◽  
Retinoic Acid Receptor Α
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