11 research outputs found
Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth
Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy
Introduction Preterm birth (PTB) may be preceded by
changes in the vaginal microflora and metabolite profiles.
Objectives We sought to characterise the metabolite
profile of cervicovaginal fluid (CVF) of pregnant women
by 1H NMR spectroscopy, and assess their predictive value
for PTB.
Methods A pair of high-vaginal swabs was obtained from
pregnant women with no evidence of clinical infection and
grouped as follows: asymptomatic low risk (ALR) women
with no previous history of PTB, assessed at 20–22 gestational
weeks, g.w., n = 83; asymptomatic high risk
(AHR) women with a previous history of PTB, assessed at
both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and
women presenting with symptoms of preterm labor (PTL)
(SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions
were dissolved in phosphate buffered saline and scanned
with a 9.4 T NMR spectrometer.
Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate,
succinate and glucose) were analysed. In
all study cohorts vaginal pH correlated with lactate integral
(r = -0.62, p\0.0001). Lactate integrals were higher in
the term ALR compared to the AHR (20–22 g.w.) women
(p = 0.003). Acetate integrals were higher in the preterm
versus term women for the AHR (20–22 g.w.) (p = 0.048)
and SYM (p = 0.003) groups; and was predictive of
PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and
delivery within 2 weeks of the index assessment (AUC
0.84; 95 % CI 0.64–1) in the SYM women, whilst other
metabolites were not.
Conclusion High CVF acetate integral of women with
symptoms of PTL appears predictive of preterm delivery,
as well as delivery within 2 weeks of presentation
Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes
Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort. A total of n = 1,789 CpG sites, corresponding to n = 1,079 genes, displayed differential methylation (q<0.1) in relation to microorganisms. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. These data support bacteria-dependent epigenetic patterning in the placenta and provide potential insight into mechanisms that associate the presence of microorganisms in the placenta to pregnancy and neonatal outcomes. This study lays the foundation for investigations of the placental microbiome and its role in placental function