Abstract
Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues. It has been evidenced that a folate deficiency (vitamin B9), or its synthetic form, folic acid (FA), in maternal diet could trigger multiple craniofacial malformations as oral clefts, tongue, or mandible abnormalities. In this study, a folic acid-deficient (FAD) diet was administered to eight-week-old C57/BL/6J female mouse for 2–16 weeks. The head symmetry, palate and nasal region were studied in 24 control and 260 experimental fetuses. Our results showed a significant reduction in the mean number of fetuses per litter according to maternal weeks on FAD diet (p < 0.01). Fetuses were affected by cleft palate (3.8%) as well as other severe congenital abnormalities, for the first time related to maternal FAD diet, as head asymmetries (4.6%), high arched palate (3.5%), nasal septum malformed (7.3%), nasopharynx duct shape (15%), and cilia and epithelium abnormalities (11.2% and 5.8%). Dysmorphologies of the nasal region were the most frequent, appearing at just four weeks following a maternal FAD diet. This is the first time that nasal region development is experimentally related to this vitamin deficiency. In conclusion, our report offers novel discoveries about the importance of maternal folate intake on midface craniofacial development of the embryos. Moreover, the longer the deficit lasts, the more serious the consequent effects appear to be.
Highlights
Craniofacial development is a complex process that begins with the participation of the frontonasal prominence and the pharyngeal arches in the earliest stages
The nasal cavities are derived from the frontonasal prominence and the palate develops from the maxillary prominences of the first pharyngeal arch [1]
The secondary palate is formed by the union, in the midline, of the palatal shelves developing from the medial aspect of the maxillary prominences [1]
Summary
Craniofacial development is a complex process that begins with the participation of the frontonasal prominence and the pharyngeal arches in the earliest stages. The nasal cavities are derived from the frontonasal prominence (including the paired lateral and medial nasal processes) and the palate develops from the maxillary prominences of the first pharyngeal arch [1]. The secondary palate is formed by the union, in the midline, of the palatal shelves developing from the medial aspect of the maxillary prominences [1]. Such structures are formed by mesoderm and neural crest cells (NCCs) that migrate from the rostral midbrain. When any alteration in the developmental process occurs, the appearance of congenital craniofacial malformations may occur due to genetic abnormalities, environmental factors, or a combination of both
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