Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Sci Rep. 2017 Sep 4;7(1):10302. doi: 10.1038/s41598-017-08057-z.
Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant ovulating (n = 20) and high- (n = 9) and low-risk (n = 16) pregnant women to probes of varying sizes and surface chemistries. We found that the motion of negatively charged, carboxylated microspheres in mucus from pregnant patients was significantly restricted compared to ovulating patients, but not significantly different between high- and low-risk pregnant women. In contrast, charged peptide probes small enough to avoid steric interactions, but sensitive to the biochemical modifications of mucus components exhibited significantly different transport profiles through mucus from high- and low-risk patients. Thus, although both microstructural rearrangements of the components of mucus as well as biochemical modifications to their adhesiveness may alter the overall permeability of the cervical mucus plug, our findings suggest that the latter mechanism plays a dominant role in the impairment of the function of this barrier during preterm birth. We expect that these probes may be readily adapted to study the mechanisms underlying disease progression on all mucosal epithelia, including those in the mouth, lungs, and gut.
早产是新生儿死亡的主要原因,常与假设由功能失调的宫颈黏液栓上细菌上升引起的羊膜内感染有关。为了研究这种功能失调,我们评估了来自非妊娠排卵(n=20)和高(n=9)和低风险(n=16)孕妇的宫颈黏液对不同大小和表面化学性质的探针的通透性。我们发现,与排卵患者相比,来自妊娠患者的带负电荷的羧基化微球在黏液中的运动受到明显限制,但高风险和低风险孕妇之间没有明显差异。相比之下,小到足以避免空间位阻相互作用但对黏液成分的生化修饰敏感的带电荷肽探针在通过高风险和低风险患者的黏液时表现出明显不同的传输谱。因此,尽管黏液成分的微观结构重排以及对其粘附性的生化修饰都可能改变宫颈黏液栓的整体通透性,但我们的研究结果表明,在后一种机制在早产期间破坏该屏障的功能中起主导作用。我们预计这些探针可以很容易地适应研究所有黏膜上皮(包括口腔、肺部和肠道)中疾病进展的机制。