scholarly journals Vaginal Microbiota, Genital Inflammation and Extracellular Matrix Remodelling Collagenase: MMP-9 in Pregnant Women With HIV, a Potential Preterm Birth Mechanism Warranting Further Exploration

2021 ◽  
Vol 11 ◽  
Author(s):  
Charlotte-Eve S. Short ◽  
Rachael A. Quinlan ◽  
Xuan Wang ◽  
Veronica Georgiana Preda ◽  
Ann Smith ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Genital Tract ◽  
Amplicon Sequencing ◽  
Vaginal Microbiota ◽  
Vaginal Fluid ◽  
Polymorphonuclear Leucocytes ◽  
Genital Tract Infection ◽  
Maternal Characteristics ◽  
Tnf Α

BackgroundPregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria.Material and MethodsCervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, combination antiretroviral therapy (cART) exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA amplicon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored.ResultsCVF was available for 50 PWLWH (108 samples) and 12 HUPW (20 samples) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p<0.001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1β, IL-8, IL-12 and TNF-α in both trimesters compared to HUPW (p ≤ 0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1β (r=0.61), IL-8 (r=0.57) and TNF-α (r=0.64), p<0.001, similarly for TIMP-1. Abundance of anaerobic pathobionts correlated with MMP-9: Gardnerella (r=0.44, p<0.001), Atopobium (r=0.33, p=0.005), and Prevotella genera (r=0.39, p<0.001). Conversely proportion of Lactobacillus genera negatively correlated with MMP-9 (rho=-0.46, p<0.001). MMP-9/TIMP-1 ratio increased with gestational age at sampling in PWLWH, but this was no longer significant after adjusting for confounders and no difference by prematurity was observed in this sub-study.ConclusionsHere we show strong correlations of MMP-9 to genital tract inflammation and sub-optimal bacterial genera in PWLWH indicating the ascending genital tract infection pathway may be a contributory mechanism to the high risk of PTB.

scholarly journals The influence of associated infection on the development of miscarriage

2020 ◽  
Vol 19 (1) ◽  
pp. 37-41
Author(s):  
S. M. Yasnikovska ◽  
A. V. Hoshovska
Keyword(s):  
Tract Infection ◽  
Pregnant Women ◽  
Genital Tract ◽  
Vaginal Microbiota ◽  
Negative Effects ◽  
Genital Tract Infection ◽  
Pregnancy And Childbirth ◽  
Lower Genital Tract ◽  
Lower Genital Tract Infection ◽  
Tract Infections

The article presents the results of a study of the vaginal microbiota in women with miscarriage in early term of gestation. It has been established that pregnant women with lower genital tract infections are at high risk for perinatal and postpartum complications. In most of them (76.0 %) there was a lack of Preconception Prevention with the study of the vaginal biotope. In pregnant women at risk of miscarriage on the background of lower genital tract infection, microbial and viral associations are more common than monoinfection. Taking into account the negative effects of lower genital tract infection on the further course of pregnancy and childbirth and the condition of newborns, at the stage of Preconception Prevention should be studied vaginal microbiota. During pregnancy, it is necessary to conduct a thorough examination of women with timely identification of risk factors for miscarriage, which include associated infections, and their adequate correction.

scholarly journals Vaginal, Cervical and Uterine pH in Women with Normal and Abnormal Vaginal Microbiota

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
Malene Risager Lykke ◽  
Naja Becher ◽  
Thor Haahr ◽  
Ebbe Boedtkjer ◽  
Jørgen Skov Jensen ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Genital Tract ◽  
Quantitative Polymerase Chain Reaction ◽  
Female Genital Tract ◽  
Uterine Cavity ◽  
Vaginal Microbiota ◽  
Reproductive Age ◽  
Ph Gradient ◽  
Increased Risk ◽  
Female Genital

Introduction: Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute to decreased fertility and increased risk of preterm birth. Therefore, we aimed to measure pH in different compartments of the female genital tract in both nonpregnant and pregnant women, stratifying into a normal and abnormal vaginal microbiota. Material and methods: In this descriptive study, we included 6 nonpregnant, 12 early-pregnant, and 8 term-pregnant women. A pH gradient was recorded with a flexible pH probe. An abnormal vaginal microbiota was diagnosed by a quantitative polymerase chain reaction technique for Atopobium vaginae; Sneathia sanguinegens; Leptotrichia amnionii; bacterial vaginosis-associated bacterium 1, 2, 3, and TM7; and Prevotella spp. among others. Results: In all participants we found the pH gradient in the lower reproductive canal to be most acidic in the lower vagina and most alkaline in the upper uterine cavity. Women with an abnormal vaginal microbiota had an increased pH in the lower vagina compared to the other groups. Conclusions: There is a pronounced pH gradient within the female genital tract. This gradient is not disrupted in women with an abnormal vaginal microbiota.

scholarly journals Early Local Cytokine Profiles in Strains of Mice with Different Outcomes from Chlamydial Genital Tract Infection

2001 ◽  
Vol 69 (6) ◽  
pp. 3556-3561 ◽  
Author(s):  
Toni Darville ◽  
Charles W. Andrews ◽  
James D. Sikes ◽  
Patrick L. Fraley ◽  
Roger. G. Rank
Keyword(s):  
Proinflammatory Cytokines ◽  
Genital Tract ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genital Tract Infection ◽  
Necrosis Factor Alpha ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Genetically Determined ◽  
Local Cytokine

ABSTRACT In this study, we expand on the examination of genetically determined differences in host responses that correlate with clearance of Chlamydia trachomatis from the genital tract. We infected C57BL/6, BALB/c, and C3H/HeN mice with the mouse pneumonitis agent of C. trachomatis (MoPn). C57BL/6 mice had the shortest course of infection (22 days) and the lowest incidence of severe hydrosalpinx. BALB/c mice also had a short course of infection (25 days), but all developed hydrosalpinx. C3H/HeN mice had the longest course of infection (38 days), and all developed severe hydrosalpinx. Determination of local cytokine responses by enzyme-linked immunosorbent assay (ELISA) of genital tract secretions revealed that the levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were significantly increased in the C57BL/6 and BALB/c strains compared to those in the C3H/HeN strain whereas the level of IL-6 was not different. The level of the neutrophil chemokine macrophage inflammatory protein 2 (MIP-2) was increased during the first week of infection in all three strains but was significantly higher in the BALB/c strain, the strain with the most rapid influx of neutrophils into the genital tract. Prolonged detection of MIP-2 in C3H/HeN mice was associated with a protracted presence of neutrophils in the genital tract. Early increases in the levels of the proinflammatory cytokines TNF-α and IL-1β are associated with earlier eradication of infection in the C57BL/6 and BALB/c strains than in the C3H/HeN strain. Increased levels of MIP-2 and neutrophils in BALB/c and C3H/HeN mice relative to C57BL/6 mice suggest that these responses may contribute to pathology.

The results of the examination of cervical-vaginal microbiota in pregnant women with threatened preterm birth using a real-time polymerase chain reaction

2018 ◽  
Vol 11_2018 ◽  
pp. 50-59 ◽  
Author(s):  
Dobrokhotova Yu.E. Dobrokhotova ◽  
Bondarenko K.R. Bondarenko ◽  
Gushchin A.E. Gushchin ◽  
Rumyantseva T.A. Rumyantseva ◽  
Dolgova T.V. Dolgova ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Preterm Birth ◽  
Pregnant Women ◽  
Real Time ◽  
Vaginal Microbiota ◽  
Chain Reaction ◽  
Polymerase Chain

scholarly journals OP02.10: Lower genital tract infection by HPV: correlation with HPV-induced trophoblastic dysfunction in late preterm birth

2014 ◽  
Vol 44 (S1) ◽  
pp. 67-67
Author(s):  
P. Breton Hernandez ◽  
M. Garcés Valenzuela ◽  
E. Moreno Romea ◽  
C. Paules Tejero ◽  
R. Benito ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Tract Infection ◽  
Genital Tract ◽  
Late Preterm ◽  
Genital Tract Infection ◽  
Late Preterm Birth ◽  
Lower Genital Tract ◽  
Lower Genital Tract Infection

Associations between second-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α and spontaneous preterm delivery in singleton pregnancies

2019 ◽  
Vol 47 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Rauf Melekoglu ◽  
Ercan Yilmaz ◽  
Osman Ciftci ◽  
Yusuf Taner Kafadar ◽  
Ebru Celik
Keyword(s):  
Preterm Birth ◽  
Amniotic Fluid ◽  
Pregnant Women ◽  
Preterm Delivery ◽  
Control Group ◽  
Second Trimester ◽  
Spontaneous Preterm Delivery ◽  
Tnf Α ◽  
Factor Α ◽  
Fluid Levels

Abstract Background We investigated the roles of inflammatory cytokines and the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family in the etiopathogenesis of spontaneous preterm delivery by comparing the ADAMTS4, ADAMTS5, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) levels in second-trimester amniotic fluid between pregnant women with preterm birth and term controls. Methods All pregnant women who underwent second-trimester amniocentesis for genetic analysis between January 1, 2016, and January 1, 2018, were enrolled in this study. From this cohort, 22 patients who subsequently experienced spontaneous preterm delivery before 34 weeks of pregnancy formed the study group, and 22 age- and body mass index (BMI)-matched patients without preterm birth constituted the control group. Results No significant differences were observed between the preterm birth and control groups in terms of age, BMI, obstetric history of preterm delivery, gestational age at amniocentesis, or indication for amniocentesis. The mean amniotic fluid levels of ADAMTS4 and ADAMTS5 were significantly increased in the preterm birth group compared to the control group (248.3±22.6 and 182.4±19.8 pg/mL, P=0.012; and 198.6±21.6 and 159.1±21.7 pg/mL, P=0.035, respectively). Significantly increased IL-6 and TNF-α levels were also detected in the amniotic fluid of women who experienced spontaneous preterm delivery, relative to controls (142.1±16.2 and 95.8±16.4 pg/mL, P<0.001; and 139.4±12.5 and 89.6±11.2 pg/mL, P<0.001, respectively). Conclusion The results of this study imply that increased mid-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α play an important role in the pathophysiology of spontaneous preterm delivery.

Cervical and Vaginal Cytokine Determinations in Pregnant Women: Methodologic Issues

2008 ◽  
Vol 9 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Susan Gennaro ◽  
Nancy Raftery ◽  
Donald Campbell ◽  
Justine Shults
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Preterm Labor ◽  
Protein Quantification ◽  
Protein Assay ◽  
Quantification Method ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Weight Method ◽  
Protein Versus

Investigations of the role cytokines play in preterm birth are complicated by a number of methodologic issues that arise as to the most feasible and efficient methods to measure cytokines. The purpose of this article is to review methodologic issues surrounding the measurement of vaginal and cervical cytokines, specifically IL-1β, IL-6, and TNF-α, in pregnant women experiencing preterm labor. Specifically, two quantification methods, weight and protein assay, and cytokine specimens from two different sites, vaginal and cervical, were compared. There were no significant correlations between cytokine levels using the protein versus weight quantification method. The weight method had more negative values and thus the protein quantification method was more accurate. There were high correlations between cervical and vaginal IL-1β levels and IL-6 levels, but cervical and vaginal TNF-α levels were not correlated.

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