Abstract
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.
Highlights
Preterm birth, defined as birth prior to 37 weeks of gestation, affects up to 18% of pregnancies world-wide, and is the leading cause of neonatal death and the second leading cause of childhood death below the age of 5 years[1]
The bacteria that infect the chorioamniotic membranes in association with preterm birth are often the same species found in the vaginal flora, suggesting that ascension occurred through the cervix[3]
In a previous study[4, 6, 7], we showed that the viscoelastic moduli of cervical mucus from patients at high risk for preterm birth are significantly lower than those measured in samples from low-risk pregnancies, and that mucus from high-risk pregnancies exhibits a significantly greater degree of spinnbarkeit under extension
Summary
Preterm birth, defined as birth prior to 37 weeks of gestation, affects up to 18% of pregnancies world-wide, and is the leading cause of neonatal death and the second leading cause of childhood death below the age of 5 years[1]. The statistical ambiguity in the stratification of low- and high-risk samples using micron-sized probes and SPT suggests that structural reconfiguration alone cannot completely account for the changes in the permeability and viscoelasticity of cervical mucus from patients at high risk for preterm birth.
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