Department of Mechanical and Aerospace Engineering, Monash University, Clayton, Victoria, Australia.
Department of Materials Science and Engineering, Monash University, Clayton, Victoria, Australia.
Nat Commun. 2024 Aug 28;15(1):7411. doi: 10.1038/s41467-024-51481-9.
The rheological properties of the extracellular fluid in the female reproductive tract vary spatiotemporally, however, the effect on the behaviour of epithelial cells that line the tract is unexplored. Here, we reveal that epithelial cells respond to the elevated viscosity of culture media by modulating their development and functionality to enhance cilia formation and coordination. Specifically, ciliation increases by 4-fold and cilia beating frequency decreases by 30% when cells are cultured at 100 mPa·s. Further, cilia manifest a coordinated beating pattern that can facilitate the formation of metachronal waves. At the cellular level, viscous loading activates the TRPV4 channel in the epithelial cells to increase intracellular Ca, subsequently decreasing the mitochondrial membrane potential level for ATP production to maintain cell viability and function. Our findings provide additional insights into the role of elevated tubal fluid viscosity in promoting ciliation and coordinating their beating-a potential mechanism to facilitate the transport of egg and embryo, suggesting possible therapeutic opportunities for infertility treatment.
女性生殖道细胞外液的流变特性具有时空变异性，但这种变异性对生殖道上皮细胞行为的影响尚未被探索。在这里，我们揭示了上皮细胞通过调节自身的发育和功能来应对培养基粘性的增加，从而增强纤毛的形成和协调。具体来说，当细胞在 100mPa·s 的粘性环境中培养时，纤毛的形成增加了 4 倍，纤毛的拍打频率降低了 30%。此外，纤毛表现出协调的拍打模式，这有助于形成蠕动波。在细胞水平上，粘性负荷激活上皮细胞中的 TRPV4 通道，增加细胞内 Ca2+，进而降低线粒体膜电位水平以产生 ATP 来维持细胞活力和功能。我们的发现为提高输卵管液粘性促进纤毛形成和协调其拍打运动的作用提供了更多的见解，这可能是促进卵子和胚胎运输的潜在机制，为不孕症的治疗提供了可能的治疗机会。
