The human placenta serves as a vital barrier between the mother and the developing fetus during pregnancy. A defect in the early development of the placenta is associated with severe pregnancy disorders. Despite its complex development, various molecular processes control placental development, and the specialization of trophoblast cells is still not fully understood. One primary obstacle is the lack of suitable cell model systems. Traditional two-dimensional (2D) cell cultures fail to mimic in vivo conditions and do not capture the intricate intercellular interactions vital for studying placental development. However, three-dimensional (3D) organoid models derived from stem cells that replicate natural cell organization and architecture have greatly improved our understanding of trophoblast behavior and its medicinal applications. Organoids with relevant phenotypes provide a valuable platform to model both placental physiology and pathology, including the modeling of placental disorders. They hold great promise for personalized medicine, improved diagnostics, and the evaluation of pharmaceutical drug efficacy and safety. This article provides a concise overview of trophoblast stem cells, trophoblast invasion, and the evolving role of organoids in gynecology.
- Keywords
- Organoids, Pregnancy complications, trophoblast invasion, trophoblast stem cells,
- MeSH
- Stem Cells * physiology MeSH
- Humans MeSH
- Organoids * physiology MeSH
- Placenta cytology physiology pathology MeSH
- Placentation physiology MeSH
- Pregnancy MeSH
- Trophoblasts * physiology MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
AIMS: To evaluate the estimated fetal radiation dose during prophylactic internal iliac arterial occlusion in patients with abnormal placenta and to estimate the risk of radiation induced cancer in child age. METHODS: Prophylactic occlusion of the internal iliac arteries during Caesarean section was performed in 42 patients with placenta praevia and/or placenta accreta spectrum. Fogarty embolectomy catheters were used for prophylactic occlusion of the internal iliac arteries. All procedures were performed in the hybrid operating room using Philips Allura Xper FD 20 X-ray system. Low dose X-ray fluoroscopy (7.5 frames per second) was used. The CODE (Conceptus dose estimation) Software was used to estimate the fetal dose and the risk of radiation induced carcinoma. RESULTS: Fluoroscopy times required for insertion of Fogarty catheters were 0.5-4.2 min (mean: 1.7 min, median: 1.5 min). The estimated radiation dose to the fetus was 0.26-3.36 mGy (mean: 1.49 mGy, median: 1.25 mGy). The risk of radiation induced cancer in child age was 0.01-0.04% (mean 0.02%, median 0.01%). One patient developed thrombosis of a common femoral artery. CONCLUSION: Prophylactic occlusion of the internal iliac arteries is a simple and safe procedure with minimal risk of complications and with a very low estimated radiation dose to the fetus.
- Keywords
- fetus radiation dose, internal iliac arteries, placenta accreta spectrum, placenta praevia, prophylactic occlusion,
- MeSH
- Balloon Occlusion * MeSH
- Cesarean Section MeSH
- Radiation Dosage MeSH
- Child MeSH
- Blood Loss, Surgical MeSH
- Humans MeSH
- Neoplasms, Radiation-Induced * MeSH
- Placentation MeSH
- Fetus MeSH
- Retrospective Studies MeSH
- Pregnancy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Plasminogen activator inhibitor type 1 (PAI-1) is the main physiologic inhibitor of fibrinolysis. However, it is also involved in many physiological processes such as extracellular matrix (ECM) proteolysis and remodeling, cell adhesion, motility, and apoptosis, angiogenesis, etc. The aim of the study was to summarize current knowledge and gain insights into the mechanisms of PAI-1 action in the processes of stromal remodeling and diseases with considerable matrix pathologies (atherosclerosis, tissue fibrosis, cancer metastasis, pregnancy related complications, etc). As a component of an early cellular response to injury, PAI-1 reacts with membrane surface proteins and participates in the initiation of intracellular signaling, specifically cytoskeletal reorganization and motility. Complexity of ECM homeostasis resides in varying relation of the plasminogen system components and other matrix constituents. Inflammatory mediators (transforming growth factor-β and interferon-γ) and hormones (angiotensin II) are in the close interdependent relation with PAI-1. Also, special attention is devoted to the role of increased PAI-1 concentrations due to the common 4G/5G polymorphism. Some of the novel mechanisms of ECM modification consider PAI-1 dependent stabilization of urokinase mediated cell adhesion, control of the vascular endothelial cadherin trafficking and interaction with endothelial cells proteasome, its relation to matrix metalloproteinase 2 and osteopontin, and oxidative inhibition by myeloperoxidase. Targeting and/or alteration of PAI-1 functions might bring benefit to the future therapeutic approaches in diseases where ECM undergoes substantial remodeling.
- Keywords
- cancer metastasis, cellular adhesion and migration, embryo implantation, fibrinolysis, tissue fibrosis,
- MeSH
- Atherosclerosis metabolism MeSH
- Extracellular Matrix metabolism MeSH
- Fibrinolysis MeSH
- Fibrosis MeSH
- Wound Healing * MeSH
- Embryo Implantation MeSH
- Myocardial Infarction metabolism MeSH
- Plasminogen Activator Inhibitor 1 metabolism MeSH
- Humans MeSH
- Neoplasm Metastasis physiopathology MeSH
- Placentation MeSH
- Cell Movement MeSH
- Vascular Remodeling * MeSH
- Signal Transduction MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Plasminogen Activator Inhibitor 1 MeSH
OBJECTIVE: Molecular pathogenesis of Down syndrome (DS) is still incompletely understood. Epigenetic mechanisms, including miRNAs gene expression regulation, belong to potential influencing factors. The aims of this study were to compare miRNAs expressions in placentas with normal and trisomic karyotype and to associate differentially expressed miRNAs with concrete biological pathways. METHODS: A total of 80 CVS samples - 41 with trisomy 21 and 39 with normal karyotype - were included in our study. Results obtained in the pilot study using real-time PCR technology and TaqMan Human miRNA Array Cards were subsequently validated on different samples using individual TaqMan miRNA Assays. RESULTS: Seven miRNAs were verified as upregulated in DS placentas (miR-99a, miR-542-5p, miR-10b, miR-125b, miR-615, let-7c and miR-654); three of these miRNAs are located on chromosome 21 (miR-99a, miR-125b and let-7c). Many essential biological processes, transcriptional regulation or apoptosis, were identified as being potentially influenced by altered miRNA levels. Moreover, miRNAs overexpressed in DS placenta apparently regulate genes involved in placenta development (GJA1, CDH11, EGF, ERVW-1, ERVFRD-1, LEP or INHA). CONCLUSION: These findings suggest the possible participation of miRNAs in Down syndrome impaired placentation and connected pregnancy pathologies. © 2016 John Wiley & Sons, Ltd.
- MeSH
- Adult MeSH
- Down Syndrome genetics metabolism MeSH
- Epidermal Growth Factor genetics MeSH
- Epigenesis, Genetic MeSH
- Gene Products, env genetics MeSH
- Inhibins genetics MeSH
- Cadherins genetics MeSH
- Connexin 43 genetics MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Leptin genetics MeSH
- Humans MeSH
- MicroRNAs genetics metabolism MeSH
- Chorionic Villi Sampling MeSH
- Pilot Projects MeSH
- Placenta metabolism MeSH
- Placentation genetics MeSH
- Case-Control Studies MeSH
- Pregnancy Proteins genetics MeSH
- Pregnancy MeSH
- Transcriptome MeSH
- Up-Regulation MeSH
- Gene Expression Regulation, Developmental genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epidermal Growth Factor MeSH
- ERVFRD-1 protein, human MeSH Browser
- Gene Products, env MeSH
- GJA1 protein, human MeSH Browser
- inhibin-alpha subunit MeSH Browser
- Inhibins MeSH
- Cadherins MeSH
- Connexin 43 MeSH
- Leptin MeSH
- MicroRNAs MeSH
- MIRN10 microRNA, human MeSH Browser
- MIRN125 microRNA, human MeSH Browser
- MIRN542 microRNA, human MeSH Browser
- MIRN615 microRNA, human MeSH Browser
- MIRN99 microRNA, human MeSH Browser
- mirnlet7 microRNA, human MeSH Browser
- osteoblast cadherin MeSH Browser
- syncytin MeSH Browser
- Pregnancy Proteins MeSH
In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.
- Keywords
- mathematical modelling, placental development, placental shape, spiral artery, stochastic dynamics,
- MeSH
- Umbilical Arteries physiology MeSH
- Models, Biological * MeSH
- Embryonic Development physiology MeSH
- Neovascularization, Physiologic physiology MeSH
- Oxygen metabolism MeSH
- Humans MeSH
- Organogenesis physiology MeSH
- Placenta embryology MeSH
- Placentation * MeSH
- Computer Simulation MeSH
- Models, Statistical MeSH
- Stochastic Processes MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Oxygen MeSH
Cellular and humoral aspects of the immune response develop sequentially in the fetus. During the ontogeny, the pluripotent stem cells emerge and differentiate into all hematopoietic lineages. Basic questions including the identification of the first lympho-hematopoietic sites, the origin of T and B lymphocytes, the development of different subpopulations of alphabeta T, gammadelta T and B lymphocytes as well as development of innate immunity and the acquisition of full immunological capacities are discussed here for swine and compared with other species. The description of related topics such as fertilization, morphogenesis, maternal-fetal-neonatal physiology and early neonatal development are also discussed.
- MeSH
- B-Lymphocytes cytology immunology metabolism MeSH
- Immunity, Cellular MeSH
- Embryo, Mammalian immunology MeSH
- Hematopoietic Stem Cells cytology immunology MeSH
- Hematopoiesis immunology MeSH
- Immune System embryology immunology MeSH
- Lymphopoiesis MeSH
- Maternal-Fetal Exchange immunology MeSH
- Morphogenesis immunology MeSH
- Placentation immunology MeSH
- Swine embryology immunology virology MeSH
- Immunity, Innate MeSH
- T-Lymphocytes cytology immunology metabolism MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Epidemiological studies have shown a clear link between fetal growth retardation and an increased propensity for later cardiovascular disease in adults. It has been hypothesized that such early fetal deprivation "programs" individuals toward a life-long metabolical "thrifty phenotype" that predisposes adults to such diseases. Here we test this hypothesis, and its possible genetic basis, in rat recombinant inbred (RI) strains that uniquely allow the longitudinal studies necessary for its testing. Placental and fetal weights were determined on day 20 of pregnancy in (at least) 6 litters from each of 25 available BXH/HXB RI strains and from their SHR and BN-Lx progenitors and were correlated with metabolic traits determined in adult rats from the same inbred lines. Quantitative trait loci (QTLs) associated with placental and fetal weights were identified by total genome scanning of RI strains using the Map Manager QTX program. Heritabilities of placental and fetal weights were 56% and 62%, respectively, and total genome scanning of RI strains revealed QTLs near the D1Rat266 marker on chromosome 1 and near the D15Rat101 marker on chromosome 15 that were significantly associated with fetal and placental weights respectively. Placental weights correlated with fetal weights (r = 0.60, P = 0.001), while reduced fetal weights correlated with increased insulin concentrations during glucose tolerance test (r = -0.71, P = 0.0001) and with increased serum triglycerides (r = -0.54, P = 0.006) in adult rats. Our results suggest that predisposition toward a thrifty phenotype associated with decreased placental weight and restricted fetal growth is in part genetically determined.
- MeSH
- Analysis of Variance MeSH
- Biomarkers analysis MeSH
- Phenotype MeSH
- Glycogen biosynthesis MeSH
- Fetal Weight physiology MeSH
- Inbreeding MeSH
- Liver metabolism MeSH
- Muscle, Skeletal metabolism MeSH
- Blood Glucose metabolism MeSH
- Rats MeSH
- Quantitative Trait Loci genetics MeSH
- Chromosome Mapping MeSH
- Metabolic Syndrome genetics metabolism physiopathology MeSH
- Placentation * MeSH
- Rats, Inbred BN MeSH
- Rats, Inbred SHR MeSH
- Recombination, Genetic MeSH
- Chromosomes, Mammalian genetics MeSH
- Pregnancy MeSH
- Triglycerides metabolism MeSH
- Organ Size MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- Glycogen MeSH
- Blood Glucose MeSH
- Triglycerides MeSH
P-glycoprotein (P-gp) is a drug efflux transporter that limits the entry of various potentially toxic drugs and xenobiotics into the fetus and is thus considered a placental protective mechanism. In this study, P-gp expression was investigated in the rat chorioallantoic placenta over the course of pregnancy. Three methods have been employed: real-time RT-PCR, western blotting and immunohistochemistry. The expression of mdr1a and mdr1b genes was demonstrated as early as on the 11th gestation day (gd) and increased with advancing gestation. Western blotting analysis revealed the presence of P-gp in the rat placenta starting from gd 13 onwards. P-gp was localized in the developing labyrinth zone of the placenta on gd 13; from gd 15 up to the term P-gp was seen as a dot like continuous line in the syncytiotrophoblast layers. Our data confirm the presence of P-gp in the rat chorioallantoic placenta starting soon after its development, which may signify the involvement of P-gp in transplacental pharmacokinetics during the whole period of placental maturing.
- MeSH
- ATP-Binding Cassette Sub-Family B Member 4 MeSH
- ATP-Binding Cassette Transporters biosynthesis genetics MeSH
- Chorion metabolism MeSH
- Immunohistochemistry MeSH
- Rats MeSH
- Membranes drug effects metabolism MeSH
- RNA, Messenger biosynthesis MeSH
- Antibodies, Monoclonal MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis MeSH
- ATP Binding Cassette Transporter, Subfamily B biosynthesis genetics MeSH
- Placenta metabolism MeSH
- Placentation MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Rats, Wistar MeSH
- Pregnancy, Animal metabolism MeSH
- Pregnancy MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- RNA, Messenger MeSH
- Antibodies, Monoclonal MeSH
- multidrug resistance protein 3 MeSH Browser
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- MeSH
- Apgar Score MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Placentation * MeSH
- Postpartum Hemorrhage MeSH
- Labor, Obstetric MeSH
- Pregnancy MeSH
- Ultrasonography * MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- English Abstract MeSH
- Journal Article MeSH
- MeSH
- Time Factors MeSH
- Embryonic and Fetal Development * MeSH
- Gestational Age MeSH
- Placentation * MeSH
- Swine embryology MeSH
- Sex Factors MeSH
- Pregnancy, Animal * MeSH
- Pregnancy MeSH
- Body Weight MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
