In the present study, we investigated the role of mechanical load as generated by amniotic fluid in the vocal fold embryogenesis. In utero, amniotic fluid flows through the laryngeal inlet down into the lungs during fetal breathing and swallowing. In a mouse model, the onset of fetal breathing coincides with epithelial lamina recanalization. The epithelial lamina is a temporal structure that is formed during early stages of the larynx development and is gradually resorbed whereby joining the upper and lower airways. Here, we show that a temporary decrease in mechanical load secondary to drainage of amniotic fluid and subsequent flow restoration, impaired timing of epithelial lamina disintegration. Moreover, re-accumulation of fluid in the laryngeal region led to VF tissue deformation triggering remodeling of the epithelium and pressure generated changes in the elastic properties of the lamina propria, as measured by atomic force microscopy. We further show that load-related structural changes were likely mediated by Piezo 1 –Yap signaling pathway in the vocal fold epithelium. Understanding the relationship between the mechanical and biological parameters in the larynx is key to gaining insights into pathogenesis of congenital laryngeal disorders as well as mechanisms of vocal fold tissue remodeling in response to mechanotransduction.

在本研究中，我们调查了由羊水产生的机械负荷在声带胚胎发生中的作用。在子宫内，在胎儿呼吸和吞咽过程中，羊水通过喉部入口向下流入肺部。在小鼠模型中，胎儿呼吸的开始与上皮层再通同时发生。上皮层是一种时间结构，在喉部发育的早期阶段形成，并逐渐被吸收，从而连接上呼吸道和下呼吸道。在这里，我们表明机械负荷的暂时减少继发于羊水引流和随后的流动恢复，损害了上皮层崩解的时间。此外，喉部区域的液体重新积聚导致 VF 组织变形，触发上皮重塑和压力产生的固有层弹性特性的变化，如原子力显微镜测量的那样。我们进一步表明，与负荷相关的结构变化可能是由声带上皮中的 Piezo 1-Yap 信号通路介导的。了解喉部机械和生物参数之间的关系是深入了解先天性喉部疾病的发病机制以及响应机械转导的声带组织重塑机制的关键。