Teratogenicity of High Vitamin A Intake

Rothman, Kenneth J.; Moore, Lynn L.; Singer, Martha R.; Nguyen, Uyen‐Sa D. T.; Mannino, Salvatore; Milunsky, Aubrey

doi:10.1056/nejm199511233332101

Cited by 651 publications

(266 citation statements)

References 19 publications

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“…Excess retinoid signaling can cause multiple developmental toxicities in various animals including humans (Rothman et al 1995;Mulder et al 2000;Degitz et al 2003). To our knowledge, only Gardiner et al (2003) have detected RAR agonistic activity in water samples, which they collected from a lake in Minnesota and a pond in California where frog malformations were routinely found; however, the causative contaminants, named as ''environmental retinoids'', were not identified.…”

Section: Resultsmentioning

confidence: 99%

Detection of Agonistic Activities Against Five Human Nuclear Receptors in River Environments of Japan Using a Yeast Two-Hybrid Assay

Inoue

Nakama

Matsui

et al. 2008

Bull Environ Contam Toxicol

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A total of 16 water samples from four rivers in Japan were examined for their agonistic activities against five human nuclear receptors (estrogen receptor [ER] alpha, thyroid hormone receptor alpha, retinoic acid receptor [RAR] alpha, retinoid X receptor alpha, and vitamin D receptor) by using a yeast two-hybrid assay. The results suggest that the river environment is contaminated with endocrine disrupting chemicals (EDCs) that can interact with a variety of nuclear receptors and that contamination with those that have RAR agonistic activity may be more serious than contamination with well-known EDCs that act as ER agonists.

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Section: Resultsmentioning

confidence: 99%

Detection of Agonistic Activities Against Five Human Nuclear Receptors in River Environments of Japan Using a Yeast Two-Hybrid Assay

Inoue

Nakama

Matsui

et al. 2008

Bull Environ Contam Toxicol

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“…Our data demonstrate that both RA and TGF-[~ inhibit the expression of Msx-1 mRNA in palate cells, and that a synergistic effect is manifested when ceils are treated simuhaneousty with both agents. Retinoic acid is a potent cleft palate-inducing teratogen in some strains of mice and is a known human teratogen (19,21,36). RA inhibits palate mesenchymal cell proliferation and prevents differentiation of palatal medial edge epithelial cells (1,43).…”

Section: Discussionmentioning

confidence: 99%

Msx-1 gene expression and regulation in embryonic palatal tissue

Nugent

Greene

1998

In Vitro Cell.Dev.Biol.-Animal

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The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.

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“…Vitamin A is an essential agent for vision, embryogenesis, reproduction, the integrity of membrane structures, epithelial differentiation, growth, and development. 51,52 Epidemiologic studies have shown a reduced risk of various chronic diseases, particularly cancers of lung, gastrointestinal tract, bladder, breast and pancreas and cardiovascular disease with dietary consumption of various carotenoids. [53][54][55][56][57][58][59][60][61] However, randomized clinical trials have not shown any consistent reduction in the incidence of cancers or cancer deaths, or of cardiovascular disease.…”

Section: Vitamin a (Retinol) And Beta-carotenementioning

confidence: 99%