scholarly journals Monitoring Maternal Beta Carotene and Retinol Consumption May Decrease the Incidence of Neurodevelopmental Disorders in Offspring

2011 ◽  
Vol 6 ◽  
pp. CMRH.S8372 ◽  
Author(s):  
Joel S. Goldberg
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Neurodevelopmental Disorders ◽  
Vitamin A Deficiency ◽  
Beta Carotene ◽  
First Trimester ◽  
Trans Retinoic Acid ◽  
First Trimester Of Pregnancy ◽  
Behavioral Teratogen ◽  
Physical And Chemical

Retinoic acids (13-cis and 13-trans) are known teratogens, and their precursor is retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association between excessive vitamin A, > 10,000 IU/day, during the first trimester of pregnancy and teratogenic effects, particularly in the central nervous system. However, vitamin A deficiency has long been known to be deleterious to the mother and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A during pregnancy that has not previously been fully appreciated. Neurodevelopmental disorders may not be apparent by macroscopic brain examination or imaging, and proving the existence of a behavioral teratogen is not straightforward. However, an excess of retinoic acid and some neurodevelopmental disorders are both associated with abnormalities in cerebellar morphology. Physical and chemical evidence strongly supports the notion that beta carotene crosses the placenta and is metabolized to retinol. Only very limited amounts of beta carotene are stored in fetal fat cells as evidenced by the fact that maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is white. Furthermore, newborns of carotenemic mothers do not share the yellow complexion of their mothers. The excess 13-trans retinoic acid derived from metabolized beta carotene in the fetus increases the concentration of the more teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted to the left. Therefore, this paper proposes that consideration be given to monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid, including nutritional supplements, dietary retinol, and beta carotene, particularly in the first trimester of pregnancy.

Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

2004 ◽  
Vol 286 (2) ◽  
pp. L437-L444 ◽  
Author(s):  
Stephen E. McGowan ◽  
Amey Jo Holmes ◽  
Jennifer Smith
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Airway Hyperresponsiveness ◽  
Vitamin A Deficiency ◽  
Elastic Fibers ◽  
Bronchial Wall ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Airway Caliber ◽  
And Function

Airway hyperresponsiveness (AHR) is influenced by structural components of the bronchial wall, including the smooth muscle and connective tissue elements and the neuromuscular function. AHR is also influenced by parenchymally derived tethering forces on the bronchial wall, which maintain airway caliber by producing outward radial traction. Our previous work has shown that vitamin A-deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in the expression and function of the muscarinic-2 receptors (M2R). We hypothesized that if decreases in radial traction from airway or parenchymal structures contributed to the VAD-related increase in AHR, then the radial traction would normalize more slowly than VAD-related alterations in neurotransmitter signaling. Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained on the VAD diet in the presence or absence of supplementation with all- trans retinoic acid (RA). VAD was associated with an approximately twofold increase in respiratory resistance and elastance compared with VAS rats. Exposure to RA for 12 days but not 4 days restored resistance and elastance to control (VAS) levels. In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression and function, which were restored after 12 days of RA supplementation. Subepithelial bronchial elastic fibers were decreased by ∼50% in VAD rats and were significantly restored by RA. The increase in AHR that is associated with VAD is accompanied by decreases in M2R expression and function that can be restored by RA and a reduction in airway elastic fibers that can be partially restored by RA.

Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment

10.1038/7417 ◽  
1999 ◽  
Vol 5 (4) ◽  
pp. 418-422 ◽  
Author(s):  
Zengquan Wang ◽  
Mohamed Boudjelal ◽  
Sewon Kang ◽  
John J. Voorhees ◽  
Gary J. Fisher
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Human Skin ◽  
Ultraviolet Irradiation ◽  
Vitamin A Deficiency ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Pre Treatment

scholarly journals Contrasting roles for all-trans retinoic acid in TGF-β–mediated induction of Foxp3 and Il10 genes in developing regulatory T cells

2009 ◽  
Vol 206 (2) ◽  
pp. 343-357 ◽  
Author(s):  
Craig L. Maynard ◽  
Robin D. Hatton ◽  
Whitney S. Helms ◽  
James R. Oliver ◽  
Charles B. Stephensen ◽  
...  
Keyword(s):  
T Cells ◽  
Retinoic Acid ◽  
T Cell ◽  
Vitamin A ◽  
Cd4 T Cells ◽  
Vitamin A Deficiency ◽  
Peripheral Tolerance ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cell Induction

Extrathymic induction of regulatory T (T reg) cells is essential to the regulation of effector T cell responses in the periphery. In addition to Foxp3, T reg cell expression of suppressive cytokines, such as IL-10, is essential for peripheral tolerance, particularly in the intestines. TGF-β has been shown to induce expression of Foxp3 as well as IL10 and the vitamin A metabolite; all-trans retinoic acid (RA [at-RA]) has been found to enhance the former. We report that in contrast to its enhancement of TGF-β–mediated Foxp3 induction, at-RA potently inhibits the TGF-β–mediated induction of Il10 in naive CD4 T cells. Thus, mucosal DC subsets that are active producers of at-RA inhibit induction of Il10 in naive CD4 T cells while promoting induction of Foxp3. Accordingly, mice with vitamin A deficiency have increased numbers of IL-10–competent T reg cells. Activation of DCs by certain Toll-like receptors (TLRs), particularly TLR9, suppresses T cell induction of Foxp3 and enables induction of Il10. Collectively, our data indicate that at-RA has reciprocal effects on the induction of Foxp3 and Il10 in developing CD4+ T reg cells and suggest that TLR9-dependent inhibition of at-RA production by antigen-presenting cells might represent one mechanism to promote the development of IL-10–expressing T cells.

scholarly journals Hypertrophy of Adipose Tissues in Quail Embryos by in ovo Injection of All-Trans Retinoic Acid

2021 ◽  
Vol 12 ◽  
Author(s):  
Dong-Hwan Kim ◽  
Joonbum Lee ◽  
Sanggu Kim ◽  
Hyun S. Lillehoj ◽  
Kichoon Lee
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Marker Gene ◽  
Marker Genes ◽  
Health Issues ◽  
Fat Cell ◽  
In Ovo ◽  
Adipose Tissues ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Excessive adipose accretion causes health issues in humans and decreases feed efficiency in poultry. Although vitamin A has been known to be involved in adipogenesis, effects of all-trans retinoic acid (atRA), as a metabolite of vitamin A, on embryonic adipose development have not been studied yet. Avian embryos are developing in confined egg environments, which can be directly modified to study effects of nutrients on embryonic adipogenesis. With the use of quail embryos, different concentrations of atRA (0 M to 10 μM) were injected in ovo at embryonic day (E) 9, and adipose tissues were sampled at E14. Percentages of fat pad weights in embryo weights were significantly increased in the group injected with 300 nM of atRA. Also, among three injection time points, E5, E7, or E9, E7 showed the most significant increase in weight and percentage of inguinal fat at E14. Injection of atRA at E7 increased fat cell size in E14 embryos with up-regulation of pro-adipogenic marker genes (Pparγ and Fabp4) and down-regulation of a preadipocyte marker gene (Dlk1) in adipose tissues. These data demonstrate that atRA promotes hypertrophic fat accretion in quail embryos, implying important roles of atRA in embryonic development of adipose tissues.

scholarly journals All-Trans-Retinoic Acid Augments the Histopathological Outcome of Neuroinflammation and Neurodegeneration in Lupus-Prone MRL/lpr Mice

2016 ◽  
Vol 65 (2) ◽  
pp. 69-81 ◽  
Author(s):  
Michelle H. Theus ◽  
Joshua B. Sparks ◽  
Xiaofeng Liao ◽  
Jingjing Ren ◽  
Xin M. Luo
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Plasma Cells ◽  
Third Ventricle ◽  
Brain Regions ◽  
Systemic Autoimmune Disease ◽  
Negative Effects ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
The Central Nervous System

Recently, we demonstrated that treatment with all- trans-retinoic acid (tRA) induced a paradoxical effect on immune activation during the development of autoimmune lupus. Here, we further describe its negative effects on mediating neuroinflammation and neurodegeneration. Female MRL/lpr mice were orally administered tRA or VARA (retinol mixed with 10% tRA) from 6 to 14 weeks of age. Both treatments had a significant effect on brain weight, which correlated with histopathological evidence of focal astrogliosis, meningitis, and ventriculitis. Infiltration of CD138- and Iba1-positve immune cells was observed in the third ventricle and meninges of treated mice that co-labeled with ICAM-1, indicating their inflammatory nature. Increased numbers of circulating plasma cells, autoantibodies, and total IgG were also apparent. IgG and C3 complement deposition in these brain regions were also prominent as was focal astrogliosis surrounding the ventricular lining and meninges. Using Fluoro-Jade staining, we further demonstrate that neuroinflammation was accompanied by neurodegeneration in the cortex of treated mice compared with vehicle controls. These findings indicate that vitamin A exposure exacerbates the immunogenic environment of the brain during the onset of systemic autoimmune disease. Vitamin A may therefore compromise the immuno-privileged nature of the central nervous system under a predisposed immunogenic environment.

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