Abstract
Most cases of congenital spinal deformities were sporadic and without strong evidence of heritability. The etiology of congenital spinal deformities is still elusive and assumed to be multi-factorial. The current study seeks to elucidate the effect of maternal vitamin A deficiency and the production of congenital spinal deformities in the offsping. Thirty two female rats were randomized into two groups: control group, which was fed a normal diet; vitamin A deficient group, which were given vitamin A-deficient diet from at least 2 weeks before mating till delivery. Three random neonatal rats from each group were killed the next day of parturition. Female rats were fed an AIN-93G diet sufficient in vitamin A to feed the rest of neonates for two weeks until euthanasia. Serum levels of vitamin A were assessed in the adult and filial rats. Anteroposterior (AP) spine radiographs were obtained at week 2 after delivery to evaluate the presence of the skeletal abnormalities especially of spinal deformities. Liver and vertebral body expression of retinaldehyde dehydrogenase (RALDHs) and RARs mRNA was assessed by reverse transcription-real time PCR. VAD neonates displayed many skeletal malformations in the cervical, thoracic, the pelvic and sacral and limbs regions. The incidence of congenital scoliosis was 13.79% (8/58) in the filial rats of vitamin A deficiency group and 0% in the control group. Furthermore, vitamin A deficiency negatively regulate the liver and verterbral body mRNA levels of RALDH1, RALDH2, RALDH3, RAR-α, RAR-β and RAR-γ. Vitamin A deficiency in pregnancy may induce congenital spinal deformities in the postnatal rats. The decreases of RALDHs and RARs mRNA expression induced by vitamin A deprivation suggest that vertebral birth defects may be caused by a defect in RA signaling pathway during somitogenesis.
Highlights
Congenital spinal deformities are not uncommon with an incidence of approximately 1 per 1,000 live births [1]
Mutations in components of these signaling pathways have been linked to several malformations, including spondylocostal dysostosis (SCDO), Alagille sydrome (AGS), abnormal vertebral segments, spinal deformities, etc. [10,11] Recent findings have suggested that disruption of the retinoic acid (RA) pathway may lead to a loss of left-right bilateral symmetry in mouse embryos [12,13,14]
The same number of neonates was found in vitamin A deficiency (VAD) and control mothers (10.1761.47 VS 9.8360.75, p.0.05; Table 1) There were 61 and 59 filial rats in VAD group and the control group, respectively
Summary
Congenital spinal deformities are not uncommon with an incidence of approximately 1 per 1,000 live births [1]. Vertebral anomalies may arise from defects in the development of the axial skeleton and are often associated with intraspinal abnormalities (e.g. myelopathy and paraplegia) and other organ defects (e.g. congenital heart disease and kidney defect) [2,3]. Recent studies have demonstrated that the axial skeleton is formed by a process known as somitogenesis during embryo development [5,6]. Mutations in components of these signaling pathways have been linked to several malformations, including spondylocostal dysostosis (SCDO), Alagille sydrome (AGS), abnormal vertebral segments (hemivertebrae,wedge vertebrae, block vertebrae), spinal deformities, etc. We hypothesize that RA signaling pathway may play a role in the development of segmentation clock that regulates the segmental structure of the vertebrate body plan during embroyogenesis
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