Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis

Noda-Nicolau, Nathália Mayumi; Tantengco, Ourlad Alzeus G.; Polettini, Jossimara; Silva, Mariana Costa; Bento, Giovana Fernanda Cosi; Cursino, Geovanna Cristofani; Marconi, Camila; Lamont, Ronald F.; Taylor, Brandie D.; Silva, Márcia Guimarães da; Jupiter, Daniel C.; Menon, Ramkumar

doi:10.3389/fmicb.2022.859732

Cited by 22 publications

(33 citation statements)

References 97 publications

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“…This supports the increased production of IL-6, IL-8, and GM-CSF in the infected VECs we observed, which are pro-in ammatory mediators that can be transported by EVs [36]. This in vitro model somewhat substantiates the ndings of our recent systematic review on genital Mycoplasma [37] where we showed that U. parvum is not a great pathogen in the cervicovaginal environment unlike other virulent species (e.g., Gardnerella). Another recent study concluded that cervicovaginal Mycoplasma infection (including Mycoplasma hominis and Ureaplasma spp.)…”

Section: Discussionsupporting

confidence: 90%

Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase

et al. 2023

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BackgroundUreaplasma, a subspecies of genital Mycoplasma is one of the most common microbes isolated from women with infection/in ammation-associated preterm labor (PTL). Mycoplasma spp. produce sialidase that cleaves sialic acid from glycans of vaginal mucous membranes and facilitates adherence and invasion of the epithelium by pathobionts, and dysregulated immune response. However, whether Ureaplasma species can induce the production of sialidase is yet to be demonstrated. We examined U. parvum-infected vaginal epithelial cells (VECs) for the production of sialidase and pro-in ammatory cytokines. MethodsImmortalized VECs were cultured in appropriate media and treated with U. parvum in a concentration of 1x 10 5 DNA copies/ml. After 24 hours of treatment, cells and media were harvested. To con rm infection and cell uptake, immunocytochemistry for multi-banded antigen (MBA) was performed. Pro-in ammatory cytokine production and protein analysis for sialidase con rmed pro-labor pathways. ResultsInfection of VECs was con rmed by the presence of intracellular MBA. Western blot analysis showed no signi cant increase in sialidase expression from U. parvum-treated VECs compared to uninfected cells. However, U. parvum infection induced increased production of GM-CSF, IL-6, and IL-8 in VECs compared to controls. ConclusionsU. parvum infection of VECs induced in ammatory imbalance associated with vaginal dysbiosis but did not alter sialidase expression at the cellular level. These data suggest that U. parvum's pathogenic effect could be propagated by locally produced pro-in ammatory cytokines and, unlike other genital mycoplasmas, may be independent of sialidase.

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Section: Discussionsupporting

confidence: 90%

Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase

et al. 2023

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“…Ureaplasma parvum and U. urealyticum were also present in the amniotic fluid of patients with preterm premature rupture of membranes (pPROM) and PTB. [26][27][28][29] The mechanism by which Ureaplasma spp. colonize, compromise the barriers of the cervix, and ascend into the amniotic cavity is not yet fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, these bacteria can breach the cervical barrier and invade the fetus within the uterine cavity. Ureaplasma parvum and U. urealyticum were also present in the amniotic fluid of patients with preterm premature rupture of membranes (pPROM) and PTB 26–29 . The mechanism by which Ureaplasma spp.…”

Section: Introductionmentioning

confidence: 99%

Modeling ascending Ureaplasma parvum infection through the female reproductive tract using vagina‐cervix‐decidua‐organ‐on‐a‐chip and feto‐maternal interface‐organ‐on‐a‐chip

et al. 2022

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Genital mycoplasmas can break the cervical barrier and cause intraamniotic infection and preterm birth. This study developed a six-chamber vagina-cervixdecidua-organ-on-a-chip (VCD-OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD-OOC were characterized by morphology and immunostaining for cell-specific markers.We transferred the media from the decidual cell chamber of the VCD-OOC to decidual cell chamber in feto-maternal interface organ-on-a-chip (FMi-OOC), which contains the fetal membrane layers. An ascending Ureaplasma parvum infection was created in VCD-OOC. U. parvum was monitored for 48 h post-infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending U. parvum infection model of PTB was developed using CD-1 mice. The cell morphology and expression of cell-specific markers in the VCD-OOC mimicked those seen in lower genital tract tissues. U. parvum reached the cervical epithelial cells and decidua within 48 h and did not cause cell death in VCD-OOC or FMi-OOC cells. U. parvum infection promoted minimal inflammation, while the combination of U. parvum and LPS promoted massive inflammation in the VCD-OOC and FMi-OOC cells. In the animal model, U. parvum vaginal inoculation of low-dose U. parvum did not result in PTB, and even a high dose had only some effects on PTB (20%). However, intra-amniotic injection of U.

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“…The bacteria associated with sPTB differ between studies and appear to vary significantly at the individual level, dependent on many factors, including specific combinations of bacteria, strains of bacteria, bacterial load, sites of bacterial localization, kinetics and timing of infection, the level of inflammation induced, as well as ethnicity and geographical region. 40,48 These differences hinder the development of accurate, universal diagnostics and effective strategies to treat women at risk of sPTB.…”

Section: Chlamydia Trachomatis Neisseria Gonorrhoeae Treponema Pallid...mentioning

confidence: 99%

Advances in mass spectrometry technologies to characterize cervicovaginal microbiome functions that impact spontaneous preterm birth

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Wilson

Hamzah

et al. 2023

American J Rep Immunol

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Preterm birth (PTB) is a leading cause of morbidity and mortality in young children. Infection is a major cause of this adverse outcome, particularly in PTBs characterised by spontaneous rupture of membranes, referred to as spontaneous (s)PTB. However, the aetiology of sPTB is not well defined and specific bacteria associated with sPTB differ between studies and at the individual level. This may be due to many factors including a lack of understanding of strain‐level differences in bacteria that influence how they function and interact with each other and the host. Metaproteomics and metabolomics are mass spectrometry‐based methods that enable the collection of detailed microbial and host functional information. Technological advances in this field have dramatically increased the resolution of these approaches, enabling the simultaneous detection of thousands of proteins or metabolites. These data can be used for taxonomic analysis of vaginal bacteria and other microbes, to understand microbiome‐host interactions, and identify diagnostic biomarkers or therapeutic targets. Although these methods have been used to assess host proteins and metabolites, few have characterized the microbial compartment in the context of pregnancy. The utilisation of metaproteomic and metabolomic‐based approaches has the potential to vastly improve our understanding of the mechanisms leading to sPTB.

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Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis

Cited by 22 publications

References 97 publications

Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase

Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase

Modeling ascending Ureaplasma parvum infection through the female reproductive tract using vagina‐cervix‐decidua‐organ‐on‐a‐chip and feto‐maternal interface‐organ‐on‐a‐chip

Advances in mass spectrometry technologies to characterize cervicovaginal microbiome functions that impact spontaneous preterm birth

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