Abstract | BACKGROUND: The eye is a very complex structure derived from the neural tube, surface ectoderm, and migratory mesenchyme from a neural crest origin. Because structures that evolve from the neural tube may be affected by a folate/ folic acid (FA) deficiency, the aim of this work was to investigate whether a maternal folic acid-deficient diet may cause developmental alterations in the mouse eye. METHODS: Female C57BL/6J mice (8 weeks old) were assigned into two different folic acid groups for periods ranging between 2 and 16 weeks. Animals were killed at gestation day 17. Hepatic folate was analyzed, and the eyes from 287 fetuses were macroscopically studied, sectioned and immunolabeled with anti- transforming growth factor (TGF)-β2 and anti-TGF-βRII. RESULTS: Mice exposed to a FA-deficient diet exhibited numerous eye macroscopic anomalies, such as anophthalmia and microphthalmia. Microscopically, the eye was the most affected organ (43.7% of the fetuses). The highest incidence of malformations occurred from the 8th week onward. A statistically significant linear association between the number of maternal weeks on the FA-deficient diet and embryonic microscopic eye malformations was observed. The optic cup derivatives and structures forming the eye anterior segment showed severe abnormalities. In addition, TGF-β2 and TGF-βRII expression in the eye was also altered. CONCLUSION: This study suggests that an adequate folic acid/ folate status plays a key role in the formation of ocular tissues and structures, whereas a vitamin deficiency is negatively associated with a normal eye development even after a short-term exposure.
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Authors | Carmen Maestro-de-las-Casas, Juliana Pérez-Miguelsanz, Yamila López-Gordillo, Estela Maldonado, Teresa Partearroyo, Gregorio Varela-Moreiras, Concepción Martínez-Álvarez |
Journal | Birth defects research. Part A, Clinical and molecular teratology
(Birth Defects Res A Clin Mol Teratol)
Vol. 97
Issue 9
Pg. 587-96
(Sep 2013)
ISSN: 1542-0760 [Electronic] United States |
PMID | 24078476
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Wiley Periodicals, Inc. |
Chemical References |
- Receptors, Transforming Growth Factor beta
- Transforming Growth Factor beta2
- Protein Serine-Threonine Kinases
- Receptor, Transforming Growth Factor-beta Type II
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Topics |
- Animals
- Case-Control Studies
- Eye Abnormalities
(etiology, pathology)
- Female
- Folic Acid Deficiency
(complications, pathology)
- Gene Expression Regulation, Developmental
(drug effects, physiology)
- Liver
(metabolism)
- Mice
- Mice, Inbred C57BL
- Pregnancy
- Protein Serine-Threonine Kinases
(metabolism)
- Receptor, Transforming Growth Factor-beta Type II
- Receptors, Transforming Growth Factor beta
(metabolism)
- Statistics, Nonparametric
- Transforming Growth Factor beta2
(metabolism)
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