-
Experimental Cell Research Feb 2019Studies have described the presence of pluripotent markers in vivo and in vitro in human amnion. However, the amnion can be divided into reflected, placental and...
Studies have described the presence of pluripotent markers in vivo and in vitro in human amnion. However, the amnion can be divided into reflected, placental and umbilical regions that are anatomically and functionally heterogeneous. Here, we evaluated the expression of pluripotency markers in tissue and cultivated cells in vitro of different regions of human amnion. To this end, we determined the presence of the core pluripotency factors OCT-4, NANOG and SOX-2 by immunofluorescence and RT-PCR and also performed transcriptome analysis of the different regions of amnion tissue. We identified the mRNA and protein of the pluripotency factors in the different regions of human amnion tissue. However, the OCT-4 and NANOG immunolocalization was cytoplasmic, whereas SOX-2 immunolocalization was nuclear regardless of the region analyzed. Moreover, we found three subpopulations of cells in the in vitro cultures of reflected and placental amnion: cells with immunostaining only in the nucleus, only in the cytoplasm, or in both compartments. Yet no statistically significant differences were found between the reflected and placental amnion. These results suggest a homogeneous distribution of the pluripotency transcription factors of the different regions of human amnion to isolate stem cells that can be used in regenerative medicine.
Topics: Amnion; Biomarkers; Cell Differentiation; Cells, Cultured; Female; Gene Expression Regulation, Developmental; Humans; Nanog Homeobox Protein; Octamer Transcription Factor-3; Placenta; Pluripotent Stem Cells; Pregnancy; SOXB1 Transcription Factors; Transcriptome
PubMed: 30557557
DOI: 10.1016/j.yexcr.2018.12.007 -
Cytokine Jul 2023The induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or...
BACKGROUND
The induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or amniotic fluid IL-6, has been described as a potential mechanism for subsequent fetal injury. The role of maternal IL-6 production and signaling in the fetal IL-6 response is currently unclear.
METHODS
Genetic and anti-IL-6 antibody strategies were used to systematically block the maternal IL-6 response during inflammation. Chorioamnionitis was induced using intraperitoneal injection of lipopolysaccharide (LPS) at mid gestation (E14.5) and late gestation (E18.5). This model was used in pregnant C57Bl/6 dams, IL6 dams, C57Bl/6 dams treated with anti-IL-6 (blocks both classical and trans-signaling) or anti-gp130 antibodies (blocks trans-signaling only) and IL6 dams. Six hours following LPS injection, maternal serum, placental tissue, amniotic fluid and fetal tissue or serum were collected. A bead-based multiplex assay was used to evaluate levels of IL-6, KC, IL-1β, TNF, IL-10, IL-22, IFN-γ, IL-13 and IL-17A.
RESULTS
Chorioamnionitis in C57Bl/6 dams was characterized by elevated maternal serum levels of IL-6, KC and IL-22 with litter loss during mid gestation. The fetal response to maternal inflammation in C57Bl/6 mice was primarily characterized by elevated levels of IL-6, KC and IL-22 in the placenta, amniotic fluid and fetus during both mid and late gestation. A global IL-6 knockout (IL6) eradicated the maternal, placental, amniotic fluid and fetal IL-6 response to LPS during mid and late gestation and improved litter survival, while minimally influencing the KC or IL-22 responses. Blocking maternal classical IL-6 signaling in C57Bl/6 dams at the time of LPS exposure diminished the maternal, placental, amniotic fluid and fetal IL-6 response during mid and late gestation, while blocking maternal IL-6 trans-signaling only affected fetal IL-6 expression. To evaluate whether maternal IL-6 was crossing the placenta and reaching the fetus, IL-6 dams were utilized in the chorioamnionitis model. IL-6 dams mounted a systemic inflammatory response following injection with LPS, characterized by elevated IL-6, KC and IL-22. IL-6 pups born to IL6 dams had decreased amniotic fluid levels of IL-6 and undetectable levels of fetal IL-6 compared to IL-6 littermate controls.
CONCLUSION
The fetal response to systemic maternal inflammation is dependent upon maternal IL-6 signaling, but maternal IL-6 is not crossing the placenta and reaching the fetus at detectable levels.
Topics: Animals; Female; Mice; Pregnancy; Amniotic Fluid; Chorioamnionitis; Disease Models, Animal; Fetal Diseases; Inflammation; Interleukin-6; Lipopolysaccharides; Placenta
PubMed: 37130487
DOI: 10.1016/j.cyto.2023.156210 -
Journal of Reproductive Immunology Dec 2022Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM),... (Review)
Review
Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM), the neutrophil infiltration into chorioamniotic membranes, is a major cause of PB. However, several cases of PB have also been reported without apparent pathogenic infection or CAM. Such cases are now attributed to "sterile inflammation." The concept of sterile inflammation has already attracted attention in various diseases, like cardiovascular diseases, diabetes, and autoimmune diseases; recently been discussed for obstetric complications such as miscarriage, PB, gestational hypertension, and gestational diabetes. Sterile inflammation is induced by alarmins, such as high-mobility group box 1 (HMGB1), interleukins (IL-33 and IL-1α), and S100 proteins, that are released by cellular damage without apparent pathogenic infection. These antigens are recognized by pattern-recognition receptors, expressed mainly on antigen-presenting cells of decidua, placenta, amnion, and myometrium, which consequently trigger inflammation. In reproduction, these alarmins are associated with the development of various pregnancy complications, including PB. In this review, we have summarized the development of PB related to acute CAM, chronic CAM, and sterile inflammation as well as proposed a new mechanism for PB that involves innate immunity, acquired immunity, and sterile inflammation.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Alarmins; Chorioamnionitis; Inflammation; Adaptive Immunity
PubMed: 36126439
DOI: 10.1016/j.jri.2022.103748 -
The Journal of Maternal-fetal &... Dec 2022Infection is considered a leading cause of fetal death, responsible for approximately 20% of cases. Such estimates are derived from the frequency of acute histological...
Infection is considered a leading cause of fetal death, responsible for approximately 20% of cases. Such estimates are derived from the frequency of acute histological chorioamnionitis and funisitis in cases of fetal death rather than direct detection of microorganisms in the fetal compartment. We report a case of clinically unexplained fetal death at 38 weeks of gestation in an uncomplicated pregnancy resulting in delivery of an appropriate-for-gestational-age fetus. The mother did not have any clinical signs of infection. Overwhelming bacterial invasion in multiple fetal organs, including the heart, liver, spleen, and kidneys, was observed despite the lack of evidence of maternal clinical infection. The bacteria were visualized by using standard histologic techniques (e.g. H&E/ tissue Gram stain) highlighting the value of autopsy in determining the cause of death.
Topics: Pregnancy; Female; Humans; Stillbirth; Chorioamnionitis; Fetal Death; Fetus; Gestational Age; Sepsis; Placenta
PubMed: 35647781
DOI: 10.1080/14767058.2022.2079404 -
American Journal of Obstetrics and... Dec 2022The assessment and management of patients with threatened midtrimester miscarriage is a clinical challenge because the etiology of this condition is poorly understood.
BACKGROUND
The assessment and management of patients with threatened midtrimester miscarriage is a clinical challenge because the etiology of this condition is poorly understood.
OBJECTIVE
This study aimed to examine the frequency of intraamniotic infection or inflammation and the effect of antibiotics in patients presenting with regular uterine contractions and intact membranes before 20 weeks of gestation.
STUDY DESIGN
This retrospective study comprised patients who met the following criteria: (1) singleton gestation, (2) gestational age before 20 weeks, (3) the presence of regular uterine contractions confirmed by a tocodynamometer (8 or more contractions in 60 minutes), (4) intact amniotic membranes, and (5) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity. Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed to detect Ureaplasma species. Amniotic fluid was tested for white blood cell counts and matrix metalloproteinase-8 concentrations to diagnose intraamniotic inflammation. Patients with intraamniotic inflammation, or intraamniotic infection, were treated with antibiotics (a combination of ceftriaxone, clarithromycin, and metronidazole). Treatment success was defined as the resolution of intraamniotic infection/inflammation at the follow-up amniocentesis or delivery after 34 weeks of gestation.
RESULTS
1) Intraamniotic inflammation was present in 88% (15/17) of patients, whereas infection was detectable in only 2 cases; 2) objective evidence of resolution of intraamniotic inflammation after antibiotic treatment was demonstrated in 100% (4/4) of patients who underwent a follow-up amniocentesis; 3) 30% (5/15) of women receiving antibiotics delivered after 34 weeks of gestation (3 of the 5 patients had a negative follow-up amniocentesis, and 2 of the women were without a follow-up amniocentesis); 4) the overall treatment success of antibiotics was 40% (6/15; 4 cases of objective evidence of resolution of intra-amniotic inflammation and 5 cases of delivery after 34 weeks of gestation).
CONCLUSION
The prevalence of intraamniotic inflammation in patients who presented with a threatened midtrimester miscarriage was 88% (15/17), and, in most cases, microorganisms could not be detected. Antibiotic treatment, administered to patients with intraamniotic inflammation, was associated with either objective resolution of intraamniotic inflammation or delivery after 34 weeks of gestation in 40% (6/15) of the cases.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Abortion, Threatened; Amniocentesis; Amniotic Fluid; Anti-Bacterial Agents; Chorioamnionitis; Inflammation; Pregnancy Trimester, Second; Retrospective Studies
PubMed: 35843271
DOI: 10.1016/j.ajog.2022.07.007 -
Pediatric Research Jan 2020Histologic chorioamnionitis is an inflammatory disorder of the placenta that commonly precedes preterm delivery. Preterm birth related to chorioamnionitis and fetal... (Review)
Review
Histologic chorioamnionitis is an inflammatory disorder of the placenta that commonly precedes preterm delivery. Preterm birth related to chorioamnionitis and fetal inflammation has been associated with a risk for serious inflammatory complications in infancy. In addition, preterm infants exposed to chorioamnionitis may be more susceptible to infection in the neonatal intensive care unit and possibly later in life. A significant body of work has established an association between chorioamnionitis and inflammatory processes. However, the potential consequences of this inflammation on postnatal immunity are less understood. In this review, we will discuss current knowledge regarding the effects of fetal exposure to inflammation on postnatal immune responses.
Topics: Adaptive Immunity; Age Factors; Animals; Chorioamnionitis; Female; Humans; Immune System; Immunity, Innate; Infant, Newborn; Infant, Premature; Inflammation Mediators; Pregnancy; Premature Birth; Risk Assessment; Risk Factors
PubMed: 31537013
DOI: 10.1038/s41390-019-0582-6 -
Stem Cells Translational Medicine Nov 2017The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human...
The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane-derived product, processed to result in a cell-free solution, while maintaining high concentrations of cell-derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA-SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA-SAM as a wound treatment using a full-thickness murine wound model. HA-SAM significantly accelerated wound closure through re-epithelialization and prevented wound contraction. HA-SAM-treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM. Stem Cells Translational Medicine 2017;6:2020-2032.
Topics: Amnion; Animals; Cells, Cultured; Cytokines; Female; Fibroblasts; Humans; Hyaluronic Acid; Hydrogels; Intercellular Signaling Peptides and Proteins; Keratinocytes; Male; Mice; Mice, Nude; Re-Epithelialization; Tissue Engineering; Tissue Scaffolds
PubMed: 28941321
DOI: 10.1002/sctm.17-0053 -
The Journal of Maternal-fetal &... Dec 2023Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial...
OBJECTIVE
Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial agents as treatment for these infections. We aimed to examine the efficacy of intravenous administration of sulbactam/ampicillin (SBT/ABPC) and azithromycin (AZM) for intra-amniotic infection in patients with preterm premature rupture of membranes (PPROM).
METHODS
This study followed a single-centered retrospective cohort design. We compared changes in interleukin 6 (IL-6) levels and the load of species DNA in the amniotic fluid between singleton pregnancy patients with intra-amniotic infection (Group A) and without either intra-amniotic inflammation (IAI) or microbial invasion of the amniotic cavity (MIAC) (Group B) who developed PPROM between week 22, day 0 and week 33, day 6 of gestation and maintained pregnancy for ≥7 d after diagnosis (August 2014 to April 2020). Patients in Group A were treated with SBT/ABPC and AZM, whereas those in Group B were treated with ABPC and AZM or clarithromycin.
RESULTS
Thirty-one patients with IAI and 48 patients without either IAI or MIAC at diagnosis of PPROM underwent pregnancy/delivery management at our hospital. Following the study population selection, we evaluated six patients in Group A and 13 patients in Group B. Amniotic fluid IL-6 concentrations at the initial amniocentesis were high, ranging from 11.7 ng/mL to 139.2 ng/mL, indicating a state of severe IAI in all six patients in Group A. In five of the six patients in Group A, the amniotic fluid cultures during the first amniocentesis included species only. In both groups, the amniotic fluid IL-6 concentration at the follow-up amniocentesis was lower than that at the initial amniocentesis (Group A: follow-up median 3.06 ng/mL [quartiles, 1.75-6.74], initial median 30.53 ng/mL [quartiles, 15.60-67.07], =.03; Group B: follow-up median 0.40 ng/mL [quartiles, 0.18-0.69], initial median 0.96 ng/mL [quartiles, 0.65-1.42], =.005); Group A showed a greater decrease than Group B ( < .001). No difference was found between the microbial loads of species DNA in the initial and follow-up amniocentesis ( = .13).
CONCLUSIONS
In patients with PPROM and intra-amniotic infection, IL-6 levels in the amniotic fluid decreased significantly from before antimicrobial administration to day 7. This decrease is thought to be mainly due to the effects of intravenous AZM. The efficacy of AZM in patients with PPROM needs to be further confirmed randomized controlled studies in the future.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Chorioamnionitis; Retrospective Studies; Premature Birth; Interleukin-6; Fetal Membranes, Premature Rupture; Anti-Bacterial Agents; Inflammation; Amniotic Fluid; Ureaplasma; DNA; Gestational Age
PubMed: 38016702
DOI: 10.1080/14767058.2023.2286189 -
Romanian Journal of Morphology and... 2017Amniotic membrane (AM) transplantation has been used successfully worldwide in ophthalmology plastic surgery for over 100 years. This review presents the histological... (Review)
Review
Amniotic membrane (AM) transplantation has been used successfully worldwide in ophthalmology plastic surgery for over 100 years. This review presents the histological and the immunohistochemical features of AM compared to those of the conjunctiva and discusses the techniques of processing and preservation, its mechanism of action in ocular reconstruction, its clinical ophthalmic indications, but also advantages and limitations of grafting with this biomaterial.
Topics: Amnion; Eye; Humans; Immunohistochemistry; Plastic Surgery Procedures
PubMed: 28730219
DOI: No ID Found -
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