Probing the potential of mucus permeability to signify preterm birth risk

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.

The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis

“…When the structure and composition of the mucus layer are aberrant, infections are likely to arise (Goldenberg et al, 2000). During pregnancy, this can be linked to preterm birth (Smith-Dupont et al, 2017). The tightness of the barrier as composed by in vitro cultured epithelial cells, can be quantified using transepithelial electrical resistance (TEER) (Gorodeski, 1996;Srinivasan B. et al, 2015).…”

The Cervicovaginal Mucus Barrier

“…Microorganisms identified in the amniotic fluid are generally similar to those found in the vagina, which suggests that the cervical canal is the most common pathway for bacteria to enter the uterine cavity [128]. As discussed above, the CMP plays an important role in preventing the ascent of infection, and a shorter, more permeable, and less mucoadhesive CMP has been found in women at high risk for preterm birth compared with those at low risk [53].…”

“…The mucus of the CMP continues to flow into the vaginal compartment throughout the pregnancy so that the CMP always contains freshly synthesized mucus. Abnormalities of the CMP, such as short length and excessive porosity, are associated with uterine infection and preterm birth [52,53]. Animal and human studies indicate that intra-amniotic infection through the cervical route triggers an inflammatory response leading to preterm labor [54].…”

“…Gel-forming mucins are mainly responsible for the viscoelastic properties of the CMP and altered permeability properties of the CMP likely result from underproduction or degradation of GFMs and/or the modification of mucin-associated glycans by bacteria usually associated with a dysbiotic vaginal flora, as discussed above. It has also been suggested that a decrease in sialic acid residues in GFM carbohydrates might increase the net charge of mucins, and thereby alter the mucoadhesive properties of the CMP and repulse cationic AMPs [53]. This could explain the insufficient antimicrobial properties of the CMP for killing some pathogenic bacteria such as Group B Streptococcus and Ureaplasma parvum [55,67].…”

The earlier the gestational age, the greater the intensity of the intra-amniotic inflammatory response in women with preterm premature rupture of membranes and amniotic fluid infection byUreaplasmaspecies

“…[7,26]. In this process, it is thought that the host defense system, such as the cervical canal and cervical mucus, plays an important role [85][86][87][88]. A solid body of evidence indicates that a short cervical length is associated with intra-amniotic infection/inflammation [68,71,[89][90][91] and development of spontaneous preterm birth [68,90,.…”