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Maternal folic acid-deficient diet causes congenital malformations in the mouse eye.

AbstractBACKGROUND:
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.
AuthorsCarmen Maestro-de-las-Casas, Juliana Pérez-Miguelsanz, Yamila López-Gordillo, Estela Maldonado, Teresa Partearroyo, Gregorio Varela-Moreiras, Concepción Martínez-Álvarez
JournalBirth 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
PMID24078476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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