Cellular immune responses in amniotic fluid of women with a sonographic short cervix

Galaz, José; Romero, Roberto; Xu, Yi; Miller, Derek; Levenson, Dustyn; Para, Robert; Varrey, Aneesha; Hsu, Richard; Tong, Anna; Hassan, Sonia S.; Hsu, Chaur‐Dong; Gomez‐Lopez, Nardhy

doi:10.1515/jpm-2020-0037

Cited by 10 publications

(5 citation statements)

References 116 publications

(103 reference statements)

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“…(28)(29)(30)(31)(32)(33)] and cellular [e.g. innate and adaptive immune cells (34)(35)(36)(37)(38)(39)(40)] components that serve as an immunological barrier against invading pathogens. In clinical medicine, amniotic fluid is utilized as a diagnostic tool for assessing intra-amniotic inflammation and/or infection (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59), a condition that is strongly associated with obstetrical disease, the most detrimental of which is preterm birth (60).…”

Section: Introductionmentioning

confidence: 99%

Does the Amniotic Fluid of Mice Contain a Viable Microbiota?

et al. 2022

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The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of fetal in utero exposure to and colonization by microorganisms and the role of intra-amniotic microorganisms in fetal immune development as well as in pregnancy outcomes. In this study, we determined whether the amniotic fluid of mice harbors a microbiota in late gestation. The profiles of the amniotic fluids of pups located proximally or distally to the cervix were characterized through quantitative real-time PCR, 16S rRNA gene sequencing, and culture (N = 21 dams). These profiles were compared to those of technical controls for bacterial and DNA contamination. The load of 16S rRNA genes in the amniotic fluid exceeded that in controls. Additionally, the 16S rRNA gene profiles of the amniotic fluid differed from those of controls, with Corynebacterium tuberculostearicum being differentially more abundant in amniotic fluid profiles; however, this bacterium was not cultured from amniotic fluid. Of the 42 attempted bacterial cultures of amniotic fluids, only one yielded bacterial growth – Lactobacillus murinus. The 16S rRNA gene of this common murine-associated bacterium was not detected in any amniotic fluid sample, suggesting it did not originate from the amniotic fluid. No differences in the 16S rRNA gene load, 16S rRNA gene profile, or bacterial culture were observed between the amniotic fluids located Proximally and distally to the cervix. Collectively, these data indicate that, although there is a modest DNA signal of bacteria in murine amniotic fluid, there is no evidence that this signal represents a viable microbiota. While this means that amniotic fluid is not a source of microorganisms for in utero colonization in mice, it may nevertheless contribute to fetal exposure to microbial components. The developmental consequences of this observation warrant further investigation.

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Section: Introductionmentioning

confidence: 99%

Does the Amniotic Fluid of Mice Contain a Viable Microbiota?

et al. 2022

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“…The risk of SPTB in asymptomatic women with a sonographic short cervix increases as cervical length decreases 14 . Previous reports have demonstrated that a shorter cervix is associated with a more severe inflammatory response in the amniotic cavity 15 . Further analysis are necessary to analyze proteins concentration in the second‐trimester amniotic fluid of women according to cervical length.…”

Section: Discussionmentioning

confidence: 99%

“… 14 Previous reports have demonstrated that a shorter cervix is associated with a more severe inflammatory response in the amniotic cavity. 15 Further analysis are necessary to analyze proteins concentration in the second‐trimester amniotic fluid of women according to cervical length. In addition, amniotic fluid protein levels may significantly fluctuate during the antenatal period, and it is not certain that the presented differences persist (or even increase) in the third trimester and contribute to preterm birth.…”

Section: Discussionmentioning

confidence: 99%

Second‐trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth

Marcellin

Batteux

Chouzenoux

et al. 2023

Acta Obstet Gynecol Scand

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Introduction:The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines TNFα, TGFβ, in asymptomatic women with and without subsequent spontaneous preterm delivery. Material and methods:We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.Clini calTr ials.gov: NCT00718705.

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“…Neutrophils represent a primary cellular component of innate immunity that protects against microorganisms invading the amniotic cavity through an array of host defense mechanisms 167 , which may include phagocytosis 168 , the release of antimicrobial products and cytokines 75 , 169 – 178 , and the formation of neutrophil extracellular traps 178 – 180 . Yet, neutrophils also form a physiological component of the AF cellular repertoire throughout pregnancy 181 ; therefore, they are present in women diagnosed with a short cervix 182 . Herein, we found that biological processes, such as neutrophil-mediated immunity, neutrophil activation, granulocyte activation, myeloid leukocyte activation, and myeloid leukocyte-mediated immunity, were impacted by protein differential abundance in women who delivered within two weeks of the diagnosis of a short cervix.…”

Section: Discussionmentioning

confidence: 99%

The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix

Gudicha

Romero

Gomez‐Lopez

et al. 2022

Sci Rep

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Preterm birth, the leading cause of perinatal morbidity and mortality, is associated with increased risk of short- and long-term adverse outcomes. For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid (AF) proteins that could predict imminent delivery in asymptomatic patients with a short cervix. This retrospective cohort study included women enrolled between May 2002 and September 2015 who were diagnosed with a sonographic short cervix (< 25 mm) at 16–32 weeks of gestation. Amniocenteses were performed to exclude intra-amniotic infection; none of the women included had clinical signs of infection or labor at the time of amniocentesis. An aptamer-based multiplex platform was used to profile 1310 AF proteins, and the differential protein abundance between women who delivered within two weeks from amniocentesis, and those who did not, was determined. The analysis included adjustment for quantitative cervical length and control of the false-positive rate at 10%. The area under the receiver operating characteristic curve was calculated to determine whether protein abundance in combination with cervical length improved the prediction of imminent preterm delivery as compared to cervical length alone. Of the 1,310 proteins profiled in AF, 17 were differentially abundant in women destined to deliver within two weeks of amniocentesis independently of the cervical length (adjusted p-value < 0.10). The decreased abundance of SNAP25 and the increased abundance of GPI, PTPN11, OLR1, ENO1, GAPDH, CHI3L1, RETN, CSF3, LCN2, CXCL1, CXCL8, PGLYRP1, LDHB, IL6, MMP8, and PRTN3 were associated with an increased risk of imminent delivery (odds ratio > 1.5 for each). The sensitivity at a 10% false-positive rate for the prediction of imminent delivery by a quantitative cervical length alone was 38%, yet it increased to 79% when combined with the abundance of four AF proteins (CXCL8, SNAP25, PTPN11, and MMP8). Neutrophil-mediated immunity, neutrophil activation, granulocyte activation, myeloid leukocyte activation, and myeloid leukocyte-mediated immunity were biological processes impacted by protein dysregulation in women destined to deliver within two weeks of diagnosis. The combination of AF protein abundance and quantitative cervical length improves prediction of the timing of delivery compared to cervical length alone, among women with a sonographic short cervix.

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Cellular immune responses in amniotic fluid of women with a sonographic short cervix

Cited by 10 publications

References 116 publications

Does the Amniotic Fluid of Mice Contain a Viable Microbiota?

Does the Amniotic Fluid of Mice Contain a Viable Microbiota?

Second‐trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth

The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix

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