-
Frontiers in Immunology 2020Chorioamnionitis, a potentially serious inflammatory complication of pregnancy, is associated with the development of an inflammatory milieu within the amniotic fluid... (Review)
Review
Chorioamnionitis, a potentially serious inflammatory complication of pregnancy, is associated with the development of an inflammatory milieu within the amniotic fluid surrounding the developing fetus. When chorioamnionitis occurs, the fetal lung finds itself in the unique position of being constantly exposed to the consequent inflammatory meditators and/or microbial products found in the amniotic fluid. This exposure results in significant changes to the fetal lung, such as increased leukocyte infiltration, altered cytokine, and surfactant production, and diminished alveolarization. These alterations can have potentially lasting impacts on lung development and function. However, studies to date have only begun to elucidate the association between such inflammatory exposures and lifelong consequences such as lung dysfunction. In this review, we discuss the pathogenesis of and fetal immune response to chorioamnionitis, detail the consequences of chorioamnionitis exposure on the developing fetal lung, highlighting the various animal models that have contributed to our current understanding and discuss the importance of fetal exposures in regard to the development of chronic respiratory disease. Finally, we focus on the clinical, basic, and therapeutic challenges in fetal inflammatory injury to the lung, and propose next steps and future directions to improve our therapeutic understanding of this important perinatal stress.
Topics: Animals; Chorioamnionitis; Female; Fetus; Humans; Lung; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 32636848
DOI: 10.3389/fimmu.2020.01285 -
The Journal of Clinical Endocrinology... Apr 2017Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix...
CONTEXT
Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion; however, epithelial to mesenchymal transition (EMT) that is also induced by MMP activation has not been investigated as a mechanism for amnion weakening.
OBJECTIVE
To measure amniotic EMT associated with vaginal delivery (VD) compared with unlabored cesarean sections (CSs), and to assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture.
FINDINGS
(1) Amnions taken from VD contained a significantly increased number of mesenchymal cells relative to epithelial cells compared with unlabored CS by fluorescence-activated cell sorting analysis (60% vs 10%); (2) tumor necrosis factor (TNF)-α stimulation of amniotic epithelial cells increased expression of the mesenchymal marker vimentin after 2 days; (3) EMT inhibitor, etodolac, significantly increased the time and mechanical pressure required to rupture the amnion; and (4) TNF-α and another pharmacologic EMT inducer, ethacridine, decreased the time and mechanical pressure required for amnion rupture, further confirming that the mesenchymal phenotype significantly weakens the amnion.
CONCLUSIONS
This work demonstrated amniotic cell EMT was associated with labor and EMT decreased the tensile strength of the amnion. These findings suggest a role for EMT in the pathophysiology of PPROM and may provide a basis for development of therapies to prevent preterm labor.
Topics: Amnion; Cyclooxygenase 2 Inhibitors; Epithelial-Mesenchymal Transition; Etodolac; Female; Fetal Membranes, Premature Rupture; Humans; Matrix Metalloproteinases; Pregnancy; Tensile Strength; Tumor Necrosis Factor-alpha
PubMed: 28388726
DOI: 10.1210/jc.2016-3150 -
Nature Sep 2019Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning. Despite its basic and clinical importance,...
Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning. Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence and limited accessibility to human embryo samples. Here we report that human pluripotent stem cells (hPSCs) in a microfluidic device recapitulate, in a highly controllable and scalable fashion, landmarks of the development of the epiblast and amniotic ectoderm parts of the conceptus, including lumenogenesis of the epiblast and the resultant pro-amniotic cavity, formation of a bipolar embryonic sac, and specification of primordial germ cells and primitive streak cells. We further show that amniotic ectoderm-like cells function as a signalling centre to trigger the onset of gastrulation-like events in hPSCs. Given its controllability and scalability, the microfluidic model provides a powerful experimental system to advance knowledge of human embryology and reproduction. This model could assist in the rational design of differentiation protocols of hPSCs for disease modelling and cell therapy, and in high-throughput drug and toxicity screens to prevent pregnancy failure and birth defects.
Topics: Amnion; Cell Differentiation; Embryo, Mammalian; Female; Germ Layers; Humans; Models, Biological; Pluripotent Stem Cells; Pregnancy; Primitive Streak
PubMed: 31511693
DOI: 10.1038/s41586-019-1535-2 -
The Cochrane Database of Systematic... Sep 2014The incidence of chorioamnionitis occurs in between eight and 12 women for every 1000 live births and 96% of cases of chorioamnionitis are due to ascending infection.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of chorioamnionitis occurs in between eight and 12 women for every 1000 live births and 96% of cases of chorioamnionitis are due to ascending infection. Following spontaneous vaginal delivery, 1% to 4% of women develop postpartum endometritis. The incidence of neonatal sepsis is 0.5% to 1% of all infants born. Maternal vaginal bacteria are the main agents for these infections. It is reasonable to speculate that prevention of maternal and neonatal infections might be possible by washing the vagina and cervix with an antibacterial agent for all women during labour. Chlorhexidine belongs to the class of compounds known as the bis-biguanides. Chlorhexidine has antibacterial action against a wide range of aerobic and anaerobic bacteria, including those implicated in peripartal infections.
OBJECTIVES
To evaluate the effectiveness and side effects of chlorhexidine vaginal douching during labour in reducing maternal and neonatal infections (excluding group B streptococcal and HIV).
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2014), reference lists of retrieved reports and journal letters and editorials.
SELECTION CRITERIA
Randomized or quasi-randomized trials comparing chlorhexidine vaginal douching during labour with placebo or other vaginal disinfectant to prevent (reduce) maternal and neonatal infections (excluding group B streptococcal and HIV).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and quality, extracted and interpreted the data. A third review author analyzed and interpreted the data. The fourth author also interpreted the data.
MAIN RESULTS
We included three studies (3012 participants). There was no evidence of an effect of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. Although the data suggest a trend in reducing postpartum endometritis, the difference was not statistically significant (three trials, 3012 women, risk ratio 0.83; 95% confidence interval 0.61 to 1.13).Assessment of the quality of the evidence using GRADE indicated that the levels of evidence for all primary outcomes and one important secondary outcome were low to moderate.
AUTHORS' CONCLUSIONS
There is no evidence to support the use of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. There is a need for a well-designed randomized controlled trial using appropriate concentration and volume of vaginal chlorhexidine irrigation solution and with adequate sample size.
Topics: Adult; Anti-Infective Agents, Local; Bacterial Infections; Chlorhexidine; Chorioamnionitis; Endometritis; Female; Humans; Infant, Newborn; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic; Vaginal Douching
PubMed: 25218725
DOI: 10.1002/14651858.CD004070.pub3 -
Placenta Jan 2018Chronic intervillositis of unknown etiology (CIUE) is a poorly understood, relatively rare condition characterized histologically by the intervillous infiltration of... (Review)
Review
Chronic intervillositis of unknown etiology (CIUE) is a poorly understood, relatively rare condition characterized histologically by the intervillous infiltration of mononuclear cells in the placenta. Clinically, CIUE is associated with poor pregnancy outcome (e.g., impaired fetal growth, preterm birth, fetal death) and high risk of recurrence in subsequent pregnancies. Because CIUE is not defined consistently, it is essential to clearly define this condition. We therefore review the published definitions of CIUE. In addition, we provide an overview of the reviewed histopathological and maternal characteristics, obstetric features, and pregnancy outcomes. Medical publication databases were searched for articles published through February 2017. Eighteen studies were included in our systematic review. The sole inclusion criterion used in all studies was the presence of intervillous infiltrates. Overall, CIUE was characterized by adverse pregnancy outcome. Miscarriage occurred in 24% of cases, with approximately half of these miscarriages defined as late. Impaired growth was commonly observed, 32.4% of pregnancies reached term, and the live birth rate was 54.9%. The high recurrence rate (25.1%) of the intervillous infiltrates in subsequent pregnancies underscores the clinical relevance of CIUE, the need for increased awareness among pathologists and clinicians, and the need for further research. Criteria for the diagnosis of CIUE are proposed and a Delphi study could be used to resolve any controversy regarding these criteria. Future studies should be designed to characterize the full clinical spectrum of CIUE.
Topics: Abortion, Spontaneous; Chorioamnionitis; Chorionic Villi; Chronic Disease; Diagnosis, Differential; Embryo Loss; Female; Fetal Death; Fetal Growth Retardation; Humans; Placenta; Placenta Diseases; Practice Guidelines as Topic; Pregnancy; Premature Birth; Prenatal Diagnosis; Recurrence; Risk; Severity of Illness Index; Stillbirth
PubMed: 29277275
DOI: 10.1016/j.placenta.2017.11.012 -
FASEB Journal : Official Publication of... Aug 2019The amnion membrane that lines the human intrauterine cavity is composed of amnion epithelial cells (AECs) connected to an extracellular matrix containing amnion...
The amnion membrane that lines the human intrauterine cavity is composed of amnion epithelial cells (AECs) connected to an extracellular matrix containing amnion mesenchymal cells (AMCs) through a basement membrane. Cellular interactions and transitions are mechanisms that facilitate membrane remodeling to maintain its integrity. Dysregulation of cellular remodeling, primarily mediated by oxidative stress (OS), is often associated with preterm birth. However, the mechanisms that maintain membrane homeostasis remain unclear. To understand these mechanisms, we developed an amnion membrane organ-on-chip (AM-OOC) and tested the interactive and transition properties of primary human AECs and AMCs under normal and OS conditions. AM-OOC contained 2 chambers connected by type IV collagen-coated microchannels, allowing independent culture conditions that permitted cellular migration and interactions. Cells grown either independently or coculture were exposed to OS inducing cigarette smoke extract, antioxidant -acetyl-l-cysteine (NAC), or both. When grown independently, AECs transitioned to AMCs and migrated, whereas AMCs migrated without transition. OS caused AECs' transition but prevented migration, whereas AMCs' migration was unhindered. Coculture of cells facilitated transition, migration, and eventual integration in the contiguous population. OS cotreatment in both chambers facilitated AECs' transition, prevented migration, and increased inflammation, a process that was prevented by NAC. AM-OOC recapitulated cellular mechanisms observed and enabled experimental manipulation of cells to determine their roles during pregnancy and parturition.-Richardson, L., Jeong, S., Kim, S., Han, A., Menon, R. Amnion membrane organ-on-chip: an innovative approach to study cellular interactions.
Topics: Amnion; Cell Communication; Cell Movement; Cells, Cultured; Coculture Techniques; Epithelial Cells; Female; Fluorescent Dyes; Humans; Inflammation Mediators; Intermediate Filaments; Keratin-18; Lab-On-A-Chip Devices; Mesenchymal Stem Cells; Oxidative Stress; Pregnancy; Vimentin
PubMed: 31039044
DOI: 10.1096/fj.201900020RR -
PloS One 2017The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally...
The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture.
Topics: Algorithms; Amnion; Cervix Uteri; Chorion; Female; Fetal Membranes, Premature Rupture; Finite Element Analysis; Gestational Age; Humans; Labor, Obstetric; Pregnancy; Stress, Mechanical; Term Birth; Uterus
PubMed: 28350838
DOI: 10.1371/journal.pone.0171588 -
International Journal of Molecular... Apr 2022Group B (GBS) is a leading cause of placental infection, termed chorioamnionitis. Chorioamnionitis is associated with an increased risk of neurobehavioral impairments,...
Group B (GBS) is a leading cause of placental infection, termed chorioamnionitis. Chorioamnionitis is associated with an increased risk of neurobehavioral impairments, such as autism spectrum disorders, which are more prominent in males than in female offspring. In a pre-clinical model of chorioamnionitis, a greater inflammatory response was observed in placenta associated with male rather than female fetuses, correlating with the severity of subsequent neurobehavioral impairments. The reason for this sex difference is not understood. Our hypothesis is that androgens upregulate the placental innate immune response in male fetuses. Lewis dams were injected daily from gestational day (G) 18 to 21 with corn oil (vehicle) or an androgen receptor antagonist (flutamide). On G 19, dams were injected with saline (control) or GBS. Maternal, fetal sera and placentas were collected for protein assays and in situ analyses. Our results showed that while flutamide alone had no effect, a decrease in placental concentration of pro-inflammatory cytokines and infiltration of polymorphonuclear cells was observed in flutamide/infected compared to vehicle/infected groups. These results show that androgens upregulate the placental innate immune response and thus may contribute to the skewed sex ratio towards males observed in several developmental impairments resulting from perinatal infection/inflammation.
Topics: Androgens; Chorioamnionitis; Female; Flutamide; Humans; Immunity, Innate; Male; Placenta; Pregnancy; Streptococcal Infections; Streptococcus agalactiae
PubMed: 35563368
DOI: 10.3390/ijms23094978 -
The Journal of Maternal-fetal &... Dec 2023Mitochondrial dysfunction was observed in acute systemic inflammatory conditions such as sepsis and might be involved in sepsis-induced multi-organ failure....
OBJECTIVE
Mitochondrial dysfunction was observed in acute systemic inflammatory conditions such as sepsis and might be involved in sepsis-induced multi-organ failure. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2), also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1), a bi-organellar protein located in the mitochondria and the nucleus, is implicated in cell respiration, survival, and response to tissue hypoxia. Recently, the reduction of the cellular CHCHD2/MNRR1 protein, as part of mitochondrial dysfunction, has been shown to play a role in the amplification of inflammatory cytokines in a murine model of lipopolysaccharide-induced systemic inflammation. The aim of this study was to determine whether the plasma concentration of CHCHD2/MNRR1 changed during human normal pregnancy, spontaneous labor at term, and clinical chorioamnionitis at term.
METHODS
We conducted a cross-sectional study that included the following groups: 1) non-pregnant women ( = 17); 2) normal pregnant women at various gestational ages from the first trimester until term ( = 110); 3) women at term with spontaneous labor ( = 50); and 4) women with clinical chorioamnionitis at term in labor ( = 25). Plasma concentrations of CHCHD2/MNRR1 were assessed by an enzyme-linked immunosorbent assay.
RESULTS
1) Pregnant women at term in labor with clinical chorioamnionitis had a significantly higher plasma CHCHD2/MNRR1 concentration than those in labor without chorioamnionitis ( = .003); 2) CHCHD2/MNRR1 is present in the plasma of healthy non-pregnant and normal pregnant women without significant differences in its plasma concentrations between the two groups; 3) there was no correlation between maternal plasma CHCHD2/MNRR1 concentration and gestational age at venipuncture; and 4) plasma CHCHD2/MNRR1 concentration was not significantly different in women at term in spontaneous labor compared to those not in labor.
CONCLUSIONS
CHCHD2/MNRR1 is physiologically present in the plasma of healthy non-pregnant and normal pregnant women, and its concentration does not change with gestational age and parturition at term. However, plasma CHCHD2/MNRR1 is elevated in women at term with clinical chorioamnionitis. CHCHD2/MNRR1, a novel bi-organellar protein located in the mitochondria and the nucleus, is released into maternal plasma during systemic inflammation.
Topics: Pregnancy; Female; Humans; Animals; Mice; Chorioamnionitis; Mitochondrial Proteins; Cross-Sectional Studies; Labor, Obstetric; Inflammation; Amniotic Fluid; DNA-Binding Proteins; Transcription Factors
PubMed: 37349086
DOI: 10.1080/14767058.2023.2222333 -
Journal of Perinatal Medicine Jul 2023Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We...
OBJECTIVES
Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We determined whether the 16S amplicon sequencing performed by a nanopore sequencing technique make possible rapid bacterial identification at the species level in intra-amniotic infection.
METHODS
Five cases of confirmed intra-amniotic infection, determined by either cultivation or 16S rDNA polymerase chain reaction (PCR) Sanger sequencing, and 10 cases of women who underwent mid-trimester genetic amniocentesis were included. DNA was extracted from amniotic fluid and PCR was performed on the full-length 16S rDNA. Nanopore sequencing was performed. The results derived from nanopore sequencing were compared with those derived from cultivation and Sanger sequencing methods.
RESULTS
Bacteria were successfully detected from amniotic fluid using nanopore sequencing in all cases of intra-amniotic infection. Nanopore sequencing identified additional bacterial species and polymicrobial infections. All patients who underwent a mid-trimester amniocentesis had negative cultures, negative 16S PCR Sanger sequencing and nanopore sequencing. Identification of the microorganisms using nanopore sequencing technique at the bacterial species level was achieved within 5-9 h from DNA extraction.
CONCLUSIONS
This is the first study demonstrating that the nanopore sequencing technique is capable of rapid diagnosis of intra-amniotic infection using fresh amniotic fluid samples.
Topics: Pregnancy; Humans; Female; Chorioamnionitis; Nanopore Sequencing; Nanopores; Amniotic Fluid; Amniocentesis; Bacteria
PubMed: 36503654
DOI: 10.1515/jpm-2022-0504