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

• Published in: Birth defects research. A Clinical and molecular teratology Vol. 97; no. 9; pp. 587 - 596
• Main Authors: Maestro-de-las-Casas, Carmen, Pérez-Miguelsanz, Juliana, López-Gordillo, Yamila, Maldonado, Estela, Partearroyo, Teresa, Varela-Moreiras, Gregorio, Martínez-Álvarez, Concepción
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Blackwell Publishing Ltd 01-09-2013; Wiley
• Subjects: Animals; Biological and medical sciences; Case-Control Studies; development; Embryology: invertebrates and vertebrates. Teratology; eye; Eye Abnormalities - etiology; Eye Abnormalities - pathology; Female; folate; folic acid deficiency; Folic Acid Deficiency - complications; Folic Acid Deficiency - pathology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Liver - metabolism; malformation; Mice; Mice, Inbred C57BL; mouse; Pregnancy; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Statistics, Nonparametric; Teratology. Teratogens; TGF-β2; TGF-βRII; Transforming Growth Factor beta2 - metabolism; Deficient diet; TGF-βRII; Congenital; Transforming growth factor; Rodentia; Nutrition disorder; B-Vitamins; Folic acid; Folate; Eye; Vertebrata; Mammalia; Mother; Mouse; Malformation; Animal; folic acid deficiency; Development; Transforming growth factor β2; TGF-β2; eye; mouse; development; folate; malformation
• ISSN: 1542-0752; 1542-0760
• DOI: 10.1002/bdra.23176

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. Birth Defects Research (Part A) 97:587–596, 2013. © 2013 Wiley Periodicals, Inc.