Vaginal Matrix Metalloproteinase Levels in Pregnant Women With Bacterial Vaginosis

Dı́az-Cueto, Laura; Cuica-Flores, Adrian; Ziga-Cordero, Francisco; Ayala-Mendez, Jose Antonio; Tena-Alavez, Gilberto; Dominguez-Lopez, Pablo; Cuevas-Antonio, Rocio; Arechavaleta-Velásco, Fabián

doi:10.1016/j.jsgi.2006.05.008

Cited by 20 publications

(18 citation statements)

References 36 publications

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“…Two of the major bacterial species associated with bacterial vaginosis, namely Gardnerella vaginalis and L. iners , appear to be either very poor d -lactic acid producers or capable of readily degrading this isomer. This provides a plausible mechanism for the observation of an association between vaginal MMP-8 levels and bacterial vaginosis (23). In a previous study, we demonstrated that in the presence of a synthetic double-stranded mimic of viral RNA, l -lactic acid strongly facilitated proinflammatory cytokine production by an in vitro -cultured vaginal epithelial cell line (16).…”

Section: Discussionmentioning

confidence: 96%

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Witkin

Mendes‐Soares

Linhares

et al. 2013

mBio

309

235

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We evaluated levels of vaginal extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP-8) in vaginal secretions in relation to the composition of vaginal bacterial communities and d- and l-lactic acid levels. The composition of vaginal bacterial communities in 46 women was determined by pyrosequencing the V1 to V3 region of 16S rRNA genes. Lactobacilli were dominant in 71.3% of the women, followed by Gardnerella (17.4%), Streptococcus (8.7%), and Enterococcus (2.2%). Of the lactobacillus-dominated communities, 51.5% were dominated by Lactobacillus crispatus, 36.4% by Lactobacillus iners, and 6.1% each by Lactobacillus gasseri and Lactobacillus jensenii. Concentrations of l-lactic acid were slightly higher in lactobacillus-dominated vaginal samples, but most differences were not statistically significant. d-Lactic acid levels were higher in samples containing L. crispatus than in those with L. iners (P < 0.0001) or Gardnerella (P = 0.0002). The relative proportion of d-lactic acid in vaginal communities dominated by species of lactobacilli was in concordance with the proportions found in axenic cultures of the various species grown in vitro. Levels of l-lactic acid (P < 0.0001) and the ratio of l-lactic acid to d-lactic acid (P = 0.0060), but not concentrations of d-lactic acid, were also correlated with EMMPRIN concentrations. Moreover, vaginal concentrations of EMMPRIN and MMP-8 levels were highly correlated (P < 0.0001). Taken together, the data suggest the relative proportion of l- to d-lactic acid isomers in the vagina may influence the extent of local EMMPRIN production and subsequent induction of MMP-8. The expression of these proteins may help determine the ability of bacteria to transverse the cervix and initiate upper genital tract infections.

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Section: Discussionmentioning

confidence: 96%

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Witkin

Mendes‐Soares

Linhares

et al. 2013

mBio

309

235

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“…This ensures that we examine the CMP and not e.g. cervicovaginal fluid, which previously has been described in several publications [16,17]. Furthermore, the extraction protocol was designed specifically for CMP MMP [14,15].…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases in the cervical mucus plug in relation to gestational age, plug compartment, and preterm labor

Becher

Hein

Danielsen

et al. 2010

Reprod Biol Endocrinol

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BackgroundHigh concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been identified in the cervical mucus plug (CMP) at term of pregnancy. Their physiological and pathophysiological implications, however, remain to be elucidated, and CMPs from preterm labor have never been examined. This study was therefore conducted to describe the concentrations of MMP-2, TIMP-1, MMP-8 and MMP-9 in the CMP in relation to gestational age, IL-8 as an indicator of inflammation, compartment of the CMP, and preterm labor.MethodsAn aliquot of the distal plug compartment facing the vaginal microflora (CMP-dist) was collected from non-pregnant (n = 15), early pregnant (n = 15) and term pregnant women (n = 15). Whole CMPs shed during active vaginal term (n = 15) and preterm (n = 4) labor were also included. Protein concentrations were determined by enzyme-linked immunosorbent assay (ELISA).ResultsMMP-2 was not detectable in the non-pregnant CMP-dists whereas high concentrations were found in early pregnancy followed by an 85% decline at term. High concentrations of TIMP-1 were found in both the non-pregnant and early pregnant CMP-dists with a 90% decline at term. Consequently, the molar TIMP/MMP ratio was 40 in the non-pregnant state and 0.2 at term. The MMP-2 and TIMP-1 concentrations were alike in the CMP-dists and the whole CMPs.MMP-8, MMP-9, and IL-8 were mainly found in the distal CMP compartment. MMP-8 and MMP-9 concentrations were several fold increased in this compartment during pregnancy compared to the non-pregnant state. In the preterm whole CMPs, MMP-8, MMP-9 and IL-8 were 2 to 5 fold increased compared to term whole CMPs.ConclusionsThese results suggest that CMP MMP-2 reflects the non-leukocyte dependent cervical remodeling that occurs in early pregnancy, whereas MMP-8 and MMP-9 are involved in the defense against ascending infections primarily located to the distal compartment of the CMP. The upregulation of MMP-8, MMP-9 and IL-8 in whole CMPs from preterm labor may indicate the involvement of an intrauterine infection.

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“… nd not determined ns not significant a only in African American women. b polymorphisms not known but enzymatic levels are higher in BV (252) (253, 254) c results in other studies do not show any association (255–258) (259) d results in other studies do not show association (260) …”

Section: Figurementioning

confidence: 93%

Vaginal and oral microbes, host genotype and preterm birth

et al. 2009

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Preterm birth (PTB) is a leading cause of infant mortality and morbidity in the U.S. and across the globe. Infection and associated inflammation are important initiators for PTB pathways; an estimated 40% of PTBs are attributed to amniochorionic-decidual or systemic inflammation. Historically, intrauterine infections have been implicated in PTB; recent evidence suggests that infections remote from the fetal site may also be causative. There is strong epidemiological evidence that bacterial vaginosis and periodontitis -- two syndromes characterized by perturbations in the normal vaginal and oral bacterial microflora respectively-- are linked to infection-associated PTB. Oral and vaginal environments are similar in their bacterial microbiology; identical bacterial species have been independently isolated in periodontitis and bacterial vaginosis. Periodontitis and bacterial vaginosis also share many behavioral and sociodemographic risk factors suggesting a possible common pathophysiology. Genetic polymorphisms in host inflammatory responses to infection are shared between bacterial vaginosis, periodontitis and PTB, suggesting common mechanisms through which host genotype modify the effect of abnormal bacterial colonization on preterm birth. We review the state of knowledge regarding the risk of PTB attributable to perturbations in bacterial flora in oral and vaginal sites and the role of host genetics in modifying the risk of infection-related PTB. We posit that bacterial species that are common in perturbed vaginal and oral sites are associated with PTB through their interaction with the host immune system.

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Vaginal Matrix Metalloproteinase Levels in Pregnant Women With Bacterial Vaginosis

Abstract: Our findings show that BV is associated with increased levels of MMP-8 in vaginal fluid. Increased production of collagen-degrading enzymes such as MMP-8 is a possible cause of spontaneous preterm delivery in pregnant women with asymptomatic BV.

Cited by 20 publications

References 36 publications

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Influence of Vaginal Bacteria andd- andl-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections

Matrix metalloproteinases in the cervical mucus plug in relation to gestational age, plug compartment, and preterm labor

Vaginal and oral microbes, host genotype and preterm birth

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