Retinoic acid downregulates microRNAs to induce abnormal development of spinal cord in spina bifida rat model.

Abstract

OBJECTS: MicroRNAs have been found in the developing central nervous system, but little is known about their functions in development, especially in the abnormal development of spinal cord in spina bifida. To this end, we have studied the mechanism of microRNAs involved in the morphogenesis of the spinal cord in all-trans-retinoic acid (RA)-treated spina bifida rat fetus. MATERIALS AND METHODS: Timed-pregnant rats were gavage-fed RA, and embryos were obtained on 13.5, 15.5, 17.5, and 19.5 days. MicroRNAs' expression profile was analyzed by Northern blot. In situ apoptosis detection and microRNA in situ hybridization methods on sections of paraffin-embedded tissues were employed to explore the mechanism. CONCLUSION: Administration of RA reduced the size of the spinal cord, probably as a consequence of increased cell death. There is a dramatic decrease in the expression of miR-9/9*, miR-124a and miR-125b, and Bcl2 and P53 as well in the sacral cord from E13.5 to E19.5 days post coitum. Our data showed that expression of these microRNAs was dysregulated in RA-treated spinal cord during embryonic development, suggesting that they may be involved in the development of the spinal cord.