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Nature Dec 2018The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with...
The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.
Topics: Cell Differentiation; Cell Movement; Chorionic Gonadotropin; DNA Methylation; Decidua; Female; Growth Differentiation Factor 15; HLA Antigens; Humans; Maternal-Fetal Relations; Models, Biological; Organoids; Placentation; Pregnancy; Pregnancy-Specific beta 1-Glycoproteins; Tissue Culture Techniques; Transcriptome; Trophoblasts
PubMed: 30487605
DOI: 10.1038/s41586-018-0753-3 -
Stem Cell Research & Therapy Jan 2022Numerous treatment strategies have so far been proposed for treating refractory thin endometrium either without or with the Asherman syndrome. Inconsistency in the... (Review)
Review
Numerous treatment strategies have so far been proposed for treating refractory thin endometrium either without or with the Asherman syndrome. Inconsistency in the improvement of endometrial thickness is a common limitation of such therapies including tamoxifen citrate as an ovulation induction agent, acupuncture, long-term pentoxifylline and tocopherol or tocopherol only, low-dose human chorionic gonadotropin during endometrial preparation, aspirin, luteal gonadotropin-releasing hormone agonist supplementation, and extended estrogen therapy. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. The mechanisms of action of cell therapy include the cytokine induction, growth factor production, natural killer cell activity reduction, Th17 and Th1 decrease, and Treg cell and Th2 increase. Since cell therapy is personalized, dynamic, interactive, and specific and could be an effective strategy. Despite its promising nature, further research is required for improving the procedure and the safety of this strategy. These methods and their results are discussed in this article.
Topics: Cell- and Tissue-Based Therapy; Chorionic Gonadotropin; Endometrium; Female; Gynatresia; Humans; Platelet-Rich Plasma
PubMed: 35090547
DOI: 10.1186/s13287-021-02698-8 -
Philosophical Transactions of the Royal... Mar 2015The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are... (Review)
Review
The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain.
Topics: Female; Fetus; Humans; Placenta; Placental Circulation; Placental Hormones; Posture; Pregnancy; Vascular Remodeling
PubMed: 25602070
DOI: 10.1098/rstb.2014.0066 -
Journal of Diabetes Research 2019Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially... (Review)
Review
Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.
Topics: Adipokines; Chorionic Gonadotropin; Cytokines; Diabetes, Gestational; Diet; Epigenesis, Genetic; Estradiol; Exosomes; Female; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Gestational Age; Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Obesity, Maternal; Placenta; Placental Hormones; Placental Lactogen; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Prolactin; Sedentary Behavior
PubMed: 31828161
DOI: 10.1155/2019/5320156 -
Emergency Medicine Clinics of North... May 2023This article reviews the use of ultrasound in pregnancy pertinent to the emergency physician. The techniques for transabdominal and transvaginal studies are detailed... (Review)
Review
This article reviews the use of ultrasound in pregnancy pertinent to the emergency physician. The techniques for transabdominal and transvaginal studies are detailed including approaches to gestational dating. Diagnosis of ectopic pregnancy is reviewed focusing on the potential pitfalls: reliance on beta-human chorionic gonadotropin, pseudogestational sac, interstitial pregnancy, and heterotopic pregnancy. Techniques for the identification of placental issues and presenting parts during the second and third trimesters are reviewed. Ultrasound is a safe and effective tool for the experienced emergency physician and is integral to providing high-quality care to pregnant women.
Topics: Pregnancy; Humans; Female; Placenta; Chorionic Gonadotropin, beta Subunit, Human; Ultrasonography; Pregnancy, Heterotopic
PubMed: 37024168
DOI: 10.1016/j.emc.2022.12.006 -
The Cochrane Database of Systematic... Mar 2017Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
To estimate and compare the accuracy of first trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome.
SEARCH METHODS
We carried out extensive literature searches including MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), and The Database of Abstracts of Reviews of Effects (the Cochrane Library 2011, Issue 7). We checked reference lists and published review articles for additional potentially relevant studies.
SELECTION CRITERIA
Studies evaluating tests of first trimester ultrasound screening, alone or in combination with first trimester serum tests (up to 14 weeks' gestation) for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more.
AUTHORS' CONCLUSIONS
Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% FPR. Although the absence of nasal bone appeared to have a high diagnostic accuracy, only five out of 10 affected Down's pregnancies were detected at a 1% FPR.
Topics: Biomarkers; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; False Positive Reactions; Female; Humans; Maternal Age; Nasal Bone; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28295158
DOI: 10.1002/14651858.CD012600 -
Frontiers in Endocrinology 2022
Topics: Endocrine System Diseases; Female; Humans; Placenta; Placental Hormones; Pre-Eclampsia; Pregnancy
PubMed: 35573985
DOI: 10.3389/fendo.2022.905829 -
International Journal of Molecular... Jul 2021Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic... (Review)
Review
Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.
Topics: Animals; Biological Evolution; Female; Humans; Placenta; Placental Hormones; Placentation; Pregnancy; Primates; Uterine Artery
PubMed: 34360862
DOI: 10.3390/ijms22158099 -
Chest Apr 2018Emerging literature suggests that sleep-disordered breathing (SDB) worsens over the course of pregnancy and is associated with adverse maternal and fetal outcomes.... (Review)
Review
Emerging literature suggests that sleep-disordered breathing (SDB) worsens over the course of pregnancy and is associated with adverse maternal and fetal outcomes. Earlier studies, using mainly snoring as a surrogate marker for SDB, have shown an increase in the prevalence of SDB during pregnancy compared with that in the pregravid state. More recently, prospective observational studies in which the investigators ascertained SDB by using complete polysomnography have shown a prevalence ranging from approximately 17% to 45% in the third trimester. Pregnancy itself can be associated with daytime hypersomnolence, so complaints of increasing fatigue and sleepiness during pregnancy are not specific for SDB. Moreover, snoring in isolation also has relatively poor sensitivity and specificity as a screening tool for diagnosing maternal SDB. The indications for screening for SDB during routine obstetric prenatal visits are still unclear, but observational studies indicate that maternal SDB is linked with the development of adverse pregnancy outcomes, such as gestational hypertension and gestational diabetes mellitus. Some studies also have identified a relationship between maternal SDB and the delivery of infants who are small for gestational age. Aside from a few small interventional studies of CPAP in pregnant patients with gestational hypertension, little currently is known about whether treatment of SDB during pregnancy improves clinical outcomes for the mother and/or baby. Additional current knowledge gaps include elucidating underlying mechanisms of maternal SDB, determining optimal treatment strategies, and understanding the trajectory of SDB after delivery.
Topics: Blood Glucose; Continuous Positive Airway Pressure; Diabetes, Gestational; Early Diagnosis; Female; Humans; Hypertension, Pregnancy-Induced; Placental Hormones; Polysomnography; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Prenatal Diagnosis; Risk Factors; Sleep Apnea Syndromes; Surveys and Questionnaires
PubMed: 29066388
DOI: 10.1016/j.chest.2017.10.011 -
Obstetrics and Gynecology May 2020
Topics: Chorionic Gonadotropin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Pregnancy
PubMed: 32332396
DOI: 10.1097/AOG.0000000000003848