Department of Bioengineering, Imperial College London, London SW72AZ,
Eur Cell Mater. 2019 Jan 15;37:23-41. doi: 10.22203/eCM.v037a03.
Congenital spine deformities may be influenced by movements in utero, but the effects of foetal immobility on spine and rib development remain unclear. The purpose of the present study was to determine (1) critical time-periods when rigid paralysis caused the most severe disruption in spine and rib development and (2) how the effects of an early, short-term immobilisation were propagated to the different features of spine and rib development. Chick embryos were immobilised once per single embryonic day (E) between E3 and E6 and harvested at E9. To assess the ontogenetic effects following single-day immobilisation, other embryos were immobilised at E4 and harvested daily between E5 and E9. Spinal curvature, vertebral shape and segmentation and rib development were analysed by optical projection tomography and histology. The results demonstrated that periods critical for movement varied for different aspects of spine and rib development. Single-day immobilisation at E3 or E4 resulted in the most pronounced spinal curvature abnormalities, multiple wedged vertebrae and segmentation defects, while single-day immobilisation at E5 led to the most severe rib abnormalities. Assessment of ontogenetic effects following single-day immobilisation at E4 revealed that vertebral segmentation defects were subsequent to earlier vertebral body shape and spinal curvature abnormalities, while rib formation (although delayed) was independent from thoracic vertebral shape or curvature changes. A day-long immobilisation in chicks severely affected spine and rib development, highlighting the importance of abnormal foetal movements at specific time-points and motivating targeted prenatal monitoring for early diagnosis of congenital scoliosis.
先天性脊柱畸形可能受子宫内运动的影响,但胎儿不动对脊柱和肋骨发育的影响仍不清楚。本研究的目的是确定(1)僵硬性瘫痪导致脊柱和肋骨发育最严重破坏的关键时期,以及(2)早期短期固定对脊柱和肋骨发育的不同特征的影响是如何传播的。鸡胚在 E3 至 E6 之间的每个胚胎日(E)固定一次,并在 E9 时收获。为了评估单次固定后的个体发育效应,其他胚胎在 E4 时固定,并在 E5 至 E9 之间每天收获。通过光学投影断层扫描和组织学分析脊柱曲率、椎体形状和分段以及肋骨发育。结果表明,对于脊柱和肋骨发育的不同方面,运动的关键时期不同。E3 或 E4 时的单日固定导致最明显的脊柱弯曲异常、多个楔形椎体和分段缺陷,而 E5 时的单日固定导致最严重的肋骨异常。评估 E4 时单日固定后的个体发育效应表明,椎体分段缺陷继发于更早的椎体形状和脊柱弯曲异常,而肋骨形成(尽管延迟)与胸椎体形状或曲率变化无关。鸡的一天固定严重影响脊柱和肋骨发育,强调了特定时间点异常胎儿运动的重要性,并为先天性脊柱侧凸的早期诊断提供了有针对性的产前监测。