A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated ‘sterile’ inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30–150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause labor-associated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.
Aging ; Cell Aging ; Cytosol ; Exosomes ; Extracellular Vesicles ; Extraembryonic Membranes ; Female ; Fetus ; Humans ; Inflammation ; Membranes ; Obstetric Labor, Premature ; Oxidative Stress ; Paracrine Communication ; Parturition ; Phenotype ; Pregnancy ; Premature Birth ; Risk Factors ; Rupture ; Telomere

Embryology is essential for the undergraduate students of medical college to understand the process and mechanisms related to both normal and abnormal development. In almost all medical colleges, anatomy class precedes embryology or at least begin simultaneously with embryology even when the anatomy related subjects including embryology are operated as integrated process during the course of basic medical science curriculum. However in the medical college of Dankook University, embryology begins in premedical course and also precedes anatomy and other anatomy related subjects. This pattern of curriculum might have its own merit and there shouldn't be any problem or difficulty in learning general embryology contents such as fertilization process, early weeks of development, congenital malformations, and fetal membranes. However, the situation is somewhat different in learning system based embryology which is focused on the development of each human system during the embryonic period. As an attempt of prerequisite learning of anatomical knowledge before beginning each chapter of system based embryology, group presentation method was newly introduced to the embryology class. In this study, a survey analysis was performed in both presentation and non-presentation group. Common survey questionnaire for both presentation and non-presentation group was composed of previous experiences on embryology related subjects, necessities of knowledge on anatomy in learner's aspect, and free comments on embryology class at large. For the presentation group, preferred methods and contents for the prerequisite learning of anatomy, relevances in the level of difficulty and length of presentation class, and preferred level of prerequisite learning of anatomy were added to survey questionnaire. In the results, necessities of knowledge on anatomy in learner's aspect between presentation and non-presentation group was different with statistical significance. In non-presentation group, it was revealed that the students themselves hardly recognize the necessities of prerequisite learning because originally they had no experience on anatomy class. Therefore, the results revealed that the precedent effort of lecturer to supply diverse chances in prerequisite learning of anatomy is a high priority especially when embryology precedes anatomy or other anatomy related subjects.
Curriculum ; Embryology* ; Extraembryonic Membranes ; Fertilization ; Humans ; Learning* ; Methods ; Teaching*

Recent studies reported increased risks for the development of allergic diseases in children after prenatal exposure to drugs. The mechanisms by which drug exposure may actually cause allergic diseases are not known. It has been suggested that these drugs promote transplacental allergen transfer to the fetus, resulting in the preservation of allergens. If transferred to the fetus, these allergens could induce a Th2-dominant immune response and allergic sensitization of the fetus. The development of the fetal immune system is influenced by the allergic state of the mother. Maternal IgE can cross fetal membranes, and a Th2-dominant phenotype in the mother can promote an allergy-prone phenotype in the fetus. The fetal immune system starts early in development but mainly matures in later trimesters. Maternal use of antibiotics during pregnancy may prove to be a risk factor for persistent wheezing and allergy development in early infancy. Paracetamol exposure during pregnancy was associated with allergic rhinitis, its use until 6 months of age was associated with allergic sensitization and a history of asthma in girls. Exposure to proton pump inhibitors (PPIs) and Histamine 2-antagonists (H2As) has been associated with an increased risk for the development of atopic dermatitis, asthma, allergic rhinitis, and especially with the development of multiple allergic diseases. Our reviews showed it is necessary to prescribe such drugs under the consultation of an expert physician and to try and reduce exposure as much as possible to prevent offspring allergies in the case of mothers with a history of allergic diseases.
Acetaminophen ; Allergens ; Anti-Bacterial Agents ; Asthma ; Child ; Dermatitis, Atopic ; Extraembryonic Membranes ; Female ; Fetus ; Histamine ; Humans ; Hypersensitivity ; Immune System ; Immunoglobulin E ; Mothers ; Phenotype ; Pregnancy ; Proton Pump Inhibitors ; Respiratory Sounds ; Rhinitis, Allergic ; Risk Factors

Chorioamnionitis is an inflammation in the fetal membranes or placenta. When chorioamnionitis develops, fetal lungs are exposed to inflammatory cytokines and mediators via amniotic fluid. Because inflammation plays a pivotal role in the development of bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, fetal lung inflammation induced by chorioamnionitis has been considered to be one of the major pathogenetic factors for BPD. Although there have been a number of studies that demonstrated the relationship between chorioamnionitis and BPD, there are still controversies on this issue. The controversies on the relationship between chorioamnionitis and BPD arise from not-unified definitions of chorioamnionitis and BPD, different study populations, and the proportion of contribution between inflammation and infectious microorganisms. The publication bias also contributes to the controversies. Clinical trials targeting chorioamnionitis or microorganisms that cause chorioamnionitis will answer on the actual relationship between chorioamnionitis and BPD and provide a novel prophylactic strategy against BPD based on that relationship.
Amniotic Fluid ; Bronchopulmonary Dysplasia* ; Chorioamnionitis* ; Cytokines ; Extraembryonic Membranes ; Female ; Humans ; Infant, Newborn ; Inflammation ; Lung ; Lung Diseases ; Placenta ; Pneumonia ; Pregnancy ; Publication Bias ; Ureaplasma

The amniotic membrane is the innermost layer of fetal membrane and is attached to the chorion in the placenta. This membrane has been used for nearly a century in varied fields such as ophthalmology, reconstructive surgery, and burn treatment. In this case report, we used a human amniotic membrane to repair an iatrogenic oroantral communication that occurred during the extraction of the patient's right upper second molar. A splint was given after the perforation was covered with human amniotic membrane and healing was clinically evaluated at various intervals. The outcome of the study revealed that the human amniotic membrane was an efficient graft material for repairing the defect caused by an iatrogenic oroantral communication following tooth extraction.
Amnion* ; Burns ; Chorion ; Extraembryonic Membranes ; Humans* ; Membranes ; Molar ; Ophthalmology ; Patient Rights ; Placenta ; Splints ; Tooth Extraction ; Transplants

Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical research. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel approach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (sodium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs. The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associated markers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcinogenicity and the use of exogenous reprogramming factors.
Amides ; pharmacology ; Animals ; Butyric Acid ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Extraembryonic Membranes ; cytology ; drug effects ; Folic Acid ; pharmacology ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Kruppel-Like Transcription Factors ; metabolism ; Mice ; Octamer Transcription Factor-3 ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Pyrazoles ; pharmacology ; Pyridines ; pharmacology ; Pyrimidines ; pharmacology ; SOXB1 Transcription Factors ; metabolism ; Thiocarbamates ; pharmacology ; Thiosemicarbazones

BACKGROUND: Recent studies have suggested that implantation site intermediate trophoblasts (ISITs) and chorionic type intermediate trophoblasts (CTITs) show different immunohistochemical findings, and that each type has specific location in placentas. However, we observed that both subtypes are intimately admixed in many areas of the placentas and both types are proliferated around the infarcts. METHODS: In order to examine the site specificity in their distribution and the changes of intermediate trophoblasts (ITs), if any, in the pre-eclamptic placentas, quantitative analyses of ISITs and CTITs using p63, CD146, placental alkaline phosphatase, human placental lactogen, and alpha-inhibin were performed in normal and pre-eclamptic placentas containing infarcts. RESULTS: In the fetal membranes of both normal and pre-eclamptic placentas, CTITs and ISITs were equally identified, forming distinct layers. ISITs were predominant in the intervillous septum and basal plate, while CTITs were predominant in the subchorionic area. At the margin of infarcts in pre-eclamptic placentas, both subtypes were increased in number, forming distinct layers. CONCLUSIONS: The subtypes of ITs do not have site specificity in placentas. Increased number of ITs and zonal distribution around infarcts suggest that CTITs and ISITs have differentiation associated relationship, and the differentiation might be related to the microenvironment of placenta, such as intraplacental oxygen concentration.
Alkaline Phosphatase ; Chorion ; Extraembryonic Membranes ; Fluconazole ; Immunohistochemistry ; Inhibins ; Oxygen ; Placenta ; Placental Lactogen ; Pre-Eclampsia ; Sensitivity and Specificity ; Trophoblasts

PURPOSE: To compare clinical outcomes after management with bed rest versus cerclage for treatment of amniotic sac bulging in the second trimester. METHODS: Women with cervical incompetence with membranes at or beyond a dilated external cervical os, before 27weeks of gestation, were treated with bed rest or emergency cerclage. We analyzed the pregnancy outcome retrospectively. 25 women underwent an emergency cerclege and 35 women underwent the bed rest. RESULTS: Gestational age at time of diagnosis was 22.40 weeks in the emergency cerclage and 22.39 weeks in the bed rest group. Mean interval from diagnosis until delivery was 8.65 weeks in the emergency cerclage group and 1.18 weeks in the bed rest group (p<0.001). Mean gestational age at delivery was 31 weeks in emergency cerclage group and 23.74 weeks in the bed rest group (p<0.001). Preterm delivery before 26 weeks and 34 weeks of gestation were significantly lower in the emergency cerclage group (p<0.001). Perinatal mortality was 17.4% in the emergency cerclage group and 48.6% in bed rest group (P=0.026). CONCLUSION: Emergency cerclage reduced preterm delivery before 26 and 34 weeks and improved perinatal outcome compared with bed rest treatment.
Bed Rest ; Emergencies ; Extraembryonic Membranes ; Female ; Gestational Age ; Humans ; Membranes ; Perinatal Mortality ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Second ; Retrospective Studies

OBJECTIVETo detect aquaporin-1 mRNA (AQP1) expression in human oligohydramnios placenta and fetal membranes.

METHODSPlacenta and fetal membranes samples were obtained from 5 women with oligohydramnios and 5 with normal amniotic fluid volume. AQP-1 mRNA expression in the tissue samples was detected by semi-quantitative RT-PCR.

RESULTSThe expression of AQP1 mRNA was significantly lower in oligohydramnios placenta than in normal pregnancy placenta at term (P<0.05), and also significantly lower in oligohydramnios fetal membranes than in normal fetal membranes at term (P<0.05).

CONCLUSIONAlterations in AQP1 mRNA expressions in human placenta and fetal membranes may play an important role in the disorder of maternal-fetal fluid exchange and amniotic fluid volume.

Adult ; Aquaporin 1 ; genetics ; metabolism ; Extraembryonic Membranes ; metabolism ; Female ; Humans ; Oligohydramnios ; metabolism ; Placenta ; metabolism ; Pregnancy ; Pregnancy Trimester, Third ; RNA, Messenger ; genetics ; metabolism ; Young Adult

OBJECTIVE: Aquaporin (AQP) 3 is a small integral membrane protein that functions as a facilitated transporter of water and glycerol. To elucidate a role of AQP3 in placenta, changes in amniotic fluid composition and fetal growth were investigated using AQP3 null mice. METHODS: Embryonic day 14,5 gestational sacs of wild-type and AQP3 kncok-out pregnant mice, thirty each, were used for this study. AQP3 localization and expression were assessed by immunohistochemistry and western blot. RESULTS: AQP3 was highly expressed in basolateral membrane of visceral yolk sac cells of fetal membrane and syncytiotrophoblast cells of labyrinthine placenta. In contrast, AQP1 was expressed in apical membrane of visceral yolk sac cells and endothelial cells lining vasculature. There was no significant difference in normal placentation and differentiation from trophoblast stem cells between wild type and AQP3 null mice. However, AQP3 null mice had increased amount of amniotic fluid per gram of body weight and decreased osmorality of amniotic fluid with low concentrations of ions and solutes in amniotic fluid. In addition, AQP3 null mice pups were smaller than CD1 wild type mice. CONCLUSION: AQP3 plays an important role in amniotic water balance and nutrient supply to developing fetus by facilitating transplacental transport of water and glycerol.
Amniotic Fluid ; Animals ; Blotting, Western ; Body Weight ; Endothelial Cells ; Extraembryonic Membranes ; Female ; Fetal Development ; Fetus ; Gestational Sac ; Glycerol ; Immunohistochemistry ; Ions ; Membrane Proteins ; Membranes ; Mice ; Placenta ; Placentation ; Stem Cells ; Trophoblasts ; Water ; Yolk Sac