scholarly journals Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ioannis Pavlidis ◽  
Owen B. Spiller ◽  
Gabriella Sammut Demarco ◽  
Heather MacPherson ◽  
Sarah E. M. Howie ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Mouse Model ◽  
Bacterial Load ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Cervical Injury ◽  
Epithelial Damage ◽  
Ureaplasma Parvum ◽  
Non Invasive ◽  
Ascending Infection

AbstractAround 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.

scholarly journals Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 313-320 ◽  
Author(s):  
Lisa F Stinson ◽  
Demelza J Ireland ◽  
Matthew W Kemp ◽  
Matthew S Payne ◽  
Sarah J Stock ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Explant Culture ◽  
Saline Control ◽  
Γ Irradiation ◽  
Ureaplasma Parvum ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Near Term

Intrauterine infection and inflammation are responsible for the majority of early (<32 weeks) spontaneous preterm births (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs:N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulatedex vivowith γ-irradiation-killedEscherichia coliapplied to the amniotic face. Membranes from near-term, ovine placentas were stimulatedin uterowith lipopolysaccharide,Ureaplasma parvumor saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3–20 h). In human membranes, the IKKβ inhibitor TPCA-1 (7 μM) and p38 MAPK inhibitor SB239063 (20 μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2in the fetal compartment. NAC (10 mM) inhibited accumulation of PGE2and IL10 only; NBDI (10 μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.

scholarly journals Utilization of Endoscopic Inoculation in a Mouse Model of Intrauterine Infection-Induced Preterm Birth: Role of Interleukin 1β1

1999 ◽  
Vol 60 (5) ◽  
pp. 1231-1238 ◽  
Author(s):  
Leonid L. Reznikov ◽  
Giamila Fantuzzi ◽  
Craig H. Selzman ◽  
Brian D. Shames ◽  
Hazel A. Barton ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Mouse Model ◽  
Intrauterine Infection

scholarly journals Cervical gene delivery of the antimicrobial peptide, Human β-defensin (HBD)-3, in a mouse model of ascending infection-related preterm birth

2019 ◽  
Author(s):  
Natalie Suff ◽  
Rajvinder Karda ◽  
Juan Antinao Diaz ◽  
Joanne Ng ◽  
Julien Baruteau ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Uterine Cavity ◽  
Preterm Births ◽  
Premature Delivery ◽  
Cervical Canal ◽  
Adeno Associated Virus ◽  
Cellular Events ◽  
Microbial Invasion ◽  
Ascending Infection ◽  
Pregnant Mice

AbstractApproximately 40% of preterm births are preceded by microbial invasion of the intrauterine space: ascent from the vagina is the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) help to constitute a barrier which prevents ascending infection. We investigated whether expression of the AMP, human β-defensin-3 (HBD3), in the cervical mucosa prevented bacterial ascent from the vagina into the uterine cavity of pregnant mice. An adeno-associated virus vector containing both the HBD3 gene and GFP transgene (AAV8 HBD3.GFP) or control (AAV8 GFP), was administered intravaginally into E13.5 pregnant mice. Ascending infection was induced at E16.5 using bioluminescent E.coli (E.coli K1 A192PP-lux2). Bioluminescence imaging showed bacterial ascent into the uterine cavity, cellular events that led to premature delivery and a reduction in pups born alive, compared with uninfected controls. In addition, a significant reduction in uterine bioluminescence in the AAV8 HBD3.GFP-treated mice was observed 24 hours post-E.coli infection, compared to AAV8 GFP treated mice, signifying reduced bacterial ascent in AAV8 HBD3.GFP-treated mice. There was also an increase in the number of living pups in AAV HBD3.GFP-treated mice. We propose that HBD3 may be considered a possible candidate for augmenting cervical innate immunity to prevent ascending infection-related preterm birth.

scholarly journals Development of a mouse model of ascending infection and preterm birth

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260370
Author(s):  
Nicholas R. Spencer ◽  
Enkhtuya Radnaa ◽  
Tuvshintugs Baljinnyam ◽  
Talar Kechichian ◽  
Ourlad Alzeus G. Tantengco ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Mouse Model ◽  
Amniotic Fluid ◽  
Imaging System ◽  
Ex Vivo ◽  
Post Inoculation ◽  
Dependent Manner ◽  
Microbial Invasion ◽  
Ascending Infection ◽  
Risk Pregnancy

Background Microbial invasion of the intraamniotic cavity and intraamniotic inflammation are factors associated with spontaneous preterm birth. Understanding the route and kinetics of infection, sites of colonization, and mechanisms of host inflammatory response is critical to reducing preterm birth risk. Objectives This study developed an animal model of ascending infection and preterm birth with live bacteria (E. coli) in pregnant CD-1 mice with the goal of better understanding the process of microbial invasion of the intraamniotic cavity and intraamniotic inflammation. Study design Multiple experiments were conducted in this study. To determine the dose of E. coli required to induce preterm birth, CD-1 mice were injected vaginally with four different doses of E. coli (103, 106, 1010, or 1011 colony forming units [CFU]) in 40 μL of nutrient broth or broth alone (control) on an embryonic day (E)15. Preterm birth (defined as delivery before E18.5) was monitored using live video. E. coli ascent kinetics were measured by staining the E. coli with lipophilic tracer DiD for visualization through intact tissue with an in vivo imaging system (IVIS) after inoculation. The E. coli were also directly visualized in reproductive tissues by staining the bacteria with carboxyfluorescein succinimidyl ester (CFSE) prior to administration and via immunohistochemistry (IHC) by staining tissues with anti-E. coli antibody. Each pup’s amniotic fluid was cultured separately to determine the extent of microbial invasion of the intraamniotic cavity at different time points. Intraamniotic inflammation resulting from E. coli invasion was assessed with IHC for inflammatory markers (TLR-4, P-NF-κB) and neutrophil marker (Ly-6G) for chorioamnionitis at 6- and 24-h post-inoculation. Results Vaginally administered E. coli resulted in preterm birth in a dose-dependent manner with higher doses causing earlier births. In ex vivo imaging and IHC detected uterine horns proximal to the cervix had increased E. coli compared to the distal uterine horns. E. coli were detected in the uterus, fetal membranes (FM), and placenta in a time-dependent manner with 6 hr having increased intensity of E. coli positive signals in pups near the cervix and in all pups at 24 hr. Similarly, E. coli grew from the cultures of amniotic fluid collected nearest to the cervix, but not from the more distal samples at 6 hr post-inoculation. At 24 hr, all amniotic fluid cultures regardless of distance from the cervix, were positive for E. coli. TLR-4 and P-NF-κB signals were more intense in the tissues where E. coli was present (placenta, FM and uterus), displaying a similar trend toward increased signal in proximal gestational sacs compared to distal at 6 hr. Ly-6G+ cells, used to confirm chorioamnionitis, were increased at 24 hr compared to 6 hr post-inoculation and control. Conclusion We report the development of mouse model of ascending infection and the associated inflammation of preterm birth. Clinically, these models can help to understand mechanisms of infection associated preterm birth, determine targets for intervention, or identify potential biomarkers that can predict a high-risk pregnancy status early in pregnancy.

Analysis risk factors for preterm births in children under care of the Department of Pediatric Rehabilitation in Bialystok

2018 ◽  
Vol 8 (2) ◽  
pp. 99-104
Author(s):  
G. Dytrych ◽  
D. Sienkiewicz
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Body Mass ◽  
Genetic Diseases ◽  
Congenital Toxoplasmosis ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Fetal Distress ◽  
Uterine Bleeding ◽  
Pediatric Rehabilitation

Introduction: Preterm birth is the birth of a baby at fewer than 37 weeks' gestational age. Preterm infants are at risk for numerous medical problems including neurological, cardiological, respiratory, and infection. Purpose: To analyse the selected risk factors of preterm births among children under the care of the Department of Pediatric Rehabilitation in Białystok Materials and methods: The retrospective study included 96 preterm children with very low body mass less than 1500 grams. All children lived in the Podlasie region of Poland. We analysed the risk factors for preterm birth based on the medical files. The detailed interview included: the course of pregnancy, diseases before pregnancy, the prevalence of genetic diseases in the nearest family, and the earlier miscarriages. Results: The intrauterine infection (20 cases), fetal distress, (19 cases), uterine bleeding (15 cases), multiple pregnancies (13 cases) were the most often risk factors of preterm births. Only a few cases concerned congenital toxoplasmosis and cytomegaly, malformation of the reproductive system, mother diseases during the pregnancy. The gender of the child did not determine the preterm birth. A significant correlation between preterm birth and the sequence of pregnancy preterm birth was related with first pregnancy in 47% of cases. There was no correlation between i. body mass and sex, ii. earlier miscarriages and preterm births. Conclusions: The risk factors of preterm births are diverse. Most common causes of preterm births were the intrauterine infection, fetal distress, and uterine bleeding.

The Alabama Preterm Birth Study: Intrauterine infection and placental histologic findings in preterm births of males and females less than 32 weeks

2006 ◽  
Vol 195 (6) ◽  
pp. 1533-1537 ◽  
Author(s):  
Robert L. Goldenberg ◽  
William W. Andrews ◽  
Ona M. Faye-Petersen ◽  
Alice R. Goepfert ◽  
Suzanne P. Cliver ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Males And Females

scholarly journals A birth population-based survey of preterm morbidity and mortality by gestational age

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaojing Guo ◽  
Xiaoqiong Li ◽  
Tingting Qi ◽  
Zhaojun Pan ◽  
Xiaoqin Zhu ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Birth Defects ◽  
Gestational Age ◽  
Death Rate ◽  
Preterm Births ◽  
Mortality Rates ◽  
Morbidity And Mortality ◽  
Hospital Death

Abstract Background Despite 15–17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai’an in 2015, an emerging prefectural region of China. Methods Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai’an Women and Children’s Hospital (HWCH) and non-HWCH hospitals in 2018–2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression. Results The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks. Conclusions The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.

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