Abstract
It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2–16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.
Highlights
Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues, such as the surface ectoderm, neural crest, mesoderm, and the pharyngeal endoderm, which provides protection and functional integration [1,2].The tongue is a complex, partially mobile organ which comprises eight bilateral muscles incompletely separated by a median septum
The decline in maternal folate levels [21,25] was accompanied by tongue dysmorphologies starting starting at 6 weeks on maternal FAD diet, but when mothers had more than two months on FAD diet at 6 weeks on maternal FAD diet, but when mothers had more than two months on FAD diet the the percentage of malformations in fetuses (56.5%) was significantly higher than the control mothers percentage of malformations in fetuses (56.5%) was significantly higher than the control mothers
The morphological and temporal differences between microglossia and aglossia we have found could indicate a dissimilar etiology of these malformations, as low levels of maternal folic acid (FA) have several possible modes of action on the development of tongue
Summary
The tongue is a complex, partially mobile organ which comprises eight bilateral muscles incompletely separated by a median septum. It is covered by a mucosa, which carries taste buds and is innervated by five cranial nerves [1,2]. The cell origin of the tongue is hybrid Both the connective tissue and vasculature derive from the cranial neural crest (NC) cells from the embryonic midbrain and the rostral first and second rhombomers of the hindbrain [2,3,4,5,6].
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