Spatiotemporal expression of leukemia inhibitory factor receptor protein during neural tube development in embryos with neural tube defects

Leukemia inhibitory factor receptor (LIFR), as a neuroregulatory cytokine receptor, generally shows a neuroprotective effect in central nervous system injuries. In this study, to understand the effect of LIFR on pathogenesis of neural tube defects, we explored spatiotemporal expression of LIFR at different stages of fetal development in normal and neural tube defect embryos. Spina bifida aperta was induced with all-trans retinoic acid on embryonic day 10 in rats, and the spatiotemporal expression of LIFR was investigated in spina bifida aperta rats and healthy rats from embryonic day 11 to 17. Real time-polymerase chain reaction and western blot assay were used to examine mRNA and protein expression of LIFR in healthy control and neural tube defect embryos. Results of the animal experiment demonstrated that expression of LIFR protein and mRNA in the spinal cords of normal rat embryos increased with embryonic development. LIFR was significantly downregulated in the spinal cords of spina bifida aperta rats compared with healthy rats from embryonic days 11 to 17. Immunohistochemical staining showed that the expression of LIFR in placenta and spinal cord in spina bifida aperta rat embryos was decreased compared with that in control embryos at embryonic day 15. Results from human embryo specimens showed that LIFR mRNA expression was significantly down-regulated in spinal cords of human fetuses with neural tube defects compared with normal controls at a gestational age of 24 to 33 weeks. The results were consistent with the down-regulation of LIFR in the animal experiments. Our study revealed spatiotemporal changes in expression of LIFR during embryonic neurulation. Thus, LIFR might play a specific role in neural tube development. All animal and human experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University, China (approval No. 2016PS106K) on February 25, 2016.