The Placenta: Basics and Clinical Significance

Foreword
Contents
Editors and Contributors
About the Editors
Contributors
Abbreviations
1: Placental Development with Histological Aspects
1.1 Introduction
1.2 Development of the Placenta
1.2.1 Prelacunar Phase (Days 5 to 8 after fertilization)
1.2.2 Lacunar Phase (Days 8 to 13 after fertilization)
1.2.3 Early Villous Phase (Days 13 to 28 p. c.)
1.2.4 Villous Phase (Day 28 p. c. to end of pregnancy)
1.3 Placental Villi
1.3.1 General Histological Structure
1.3.2 Syncytiotrophoblast
In Vitro Culture and Syncytiotrophoblast
Structure and Function of the Syncytiotrophoblast
Protrusions of the Syncytiotrophoblast
1.3.3 Villous Cytotrophoblast (Langhans Cell)
1.3.4 Villous Stroma
1.3.5 Placental Blood Vessels
1.4 Architecture of the Villous Tree
1.4.1 Mesenchymal Villi
1.4.2 Immature Intermediate Villi
1.4.3 Stem Villi
1.4.4 Mature Intermediate Villi
1.4.5 Terminal Villi
1.5 Extravillous Trophoblast
1.5.1 Interstitial Trophoblast
1.5.2 Endoglandular Trophoblast
1.5.3 Endovascular Trophoblast
Endoarterial Trophoblast
Endovenous Trophoblast
1.5.4 Endolymphatic Trophoblast
1.5.5 General Considerations on Trophoblast Invasion
1.5.6 Maternal Perfusion of the Placenta
In the First Trimester
In the Second and Third Trimester
1.5.7 Formation of the Chorion laeve (fetal membranes)
References
2: Immunology of the Fetomaternal Border
2.1 Background
2.2 Immunology of the Endometrium
2.3 Immunology of Pregnancy
2.3.1 Problems
2.3.2 Fetomaternal Interfaces
2.3.3 Pregnancy: A Th2 Phenomenon
2.3.4 Regulatory T Cells
2.3.5 γδ-T Cells
2.3.6 Natural Killer Cells
Uterine NK Cells
2.3.7 Uterine CD14+ Cells
2.3.8 Trophoblastic Immunoregulatory Factors
HLA Class Ib
Indoleamine 2,3-dioxygenase (IDO)
2.3.9 Hormones
Human Chorionic Gonadotropin (hCG)
2.3.10 Other Selected Pregnancy-promoting Mechanisms
Fas/Fas Ligand
Galectin-1
Trophoblastic Extracellular Vesicles
2.4 Summary and Conclusion
References
3: Placental Morphology
3.1 Morphology of the Placenta
3.1.1 Introduction
3.1.2 Villous Development
3.1.3 Development of Cell Columns for Trophoblast Invasion
3.1.4 Structures on the Villous Surface
3.2 Histopathology of the Placenta for Gynecologists
3.2.1 Introduction
3.2.2 First Trimester (Abortion)
Abortion with and Without Developmental Aberration
Question About Hydatidiform Mole
Answers and Evidence from Examination of Abortion Material
3.2.3 Second Trimester (Hydrops Fetalis, Infection and Inflammation)
Hydrops of Fetus and Placenta
Immunological Hydrops in Blood Group Incompatibility
Hydrops as A Result of Infection (Fifth Disease, Erythema infectiosum)
Placentitis
(Acute) Inflammation of the Chorionic Villi with Evidence of Pathogens
(Chronic) Inflammation of the Chorionic Villi Without Evidence of Pathogens
Chorioamnionitis (Amniotic Infection Syndrome)
Umbilical Cord Infection
Answers and Evidence from Examination of Placentas in Preterm Delivery
3.2.4 Third Trimester (Circulatory and Maturation Disorders)
Maternal Circulatory Disorder
Preeclampsia
Premature Placental Abruption
Fetal Circulatory Disorder
Endangiopathy Obliterans
Hereditary Thrombophilias
Umbilical Cord Complications
Maturation Disorder
Intermediate Villus Deficiency
Chorangiosis
Maturation Retardation
Terminal Villus Deficiency
Responses and Evidence from Studies of Small-for-date Newborns and Stillbirths
3.2.5 Postpartum Period
Placenta Accreta or Increta
Neoplasia
Malignant Degeneration of the Chorial Tissue
Metastases to the Placenta
Twins
Chorionicity and Zygosity
Fetofetal Transfusion
3.3 Biobanking
3.3.1 Introduction
What Exactly Is Pre-analysis?
3.3.2 Variables Affecting the Composition of a Sample
Variables Before Sampling
Variables After Sampling
3.3.3 Collection or Biobank?
Definition of Biobanks
Advantages of Biobanks
Further Readings
Further Reading on Section 3.2
4: Placental Function—Nutrient Transport—Gas Exchange
4.1 General Functions of the Placenta
4.2 Nutrient Transport Across the Placenta
4.2.1 Transport of Lipids and Fatty Acids
4.2.2 Transport of Glucose
4.2.3 Transport of Proteins and Amino Acids
4.2.4 Transport of Minerals and Trace Elements
4.3 Maternofetal Gas Exchange
References
5: Endocrinology of the Placenta
5.1 Introduction
5.2 Steroid Hormones
5.2.1 Progesterone
5.2.2 Estrogens
5.2.3 Glucocorticoids
5.3 Peptide Hormones
5.3.1 Human Chorionic Gonadotropin (hCG)
5.3.2 Leptin
5.3.3 Corticotrophin Releasing Hormone (CRH)
5.3.4 Placental Lactogen (hPL) and Placental Growth Hormone (hPGH)
5.3.5 Summary
References
6: Teratology
6.1 Introduction
6.2 Congenital Anomalies Historically
6.3 Congenital Anomalies Today
6.4 Basic Risk
6.5 Medication and Pregnancy
6.6 Placenta and Teratology
6.6.1 The Sensitivity of the Embryo to Toxic Influences Depends on the Genotype
6.6.2 The Sensitivity of the Embryo to Toxic Influences Depends on Its Stage of Development
6.6.3 Different Embryotoxic Influences Affect (Embryonic) Development via Relatively Few Specific Mechanisms
6.6.4 After Exposure to Teratogens, Different Developmental Courses Are Possible in Principle
6.6.5 The Way in Which Toxic Influences Reach the Embryo/Fetus Depends on Their Physical and Chemical Properties
6.6.6 Dose-response Relationships Apply in Teratology as Elsewhere in Pharmacology and Toxicology
6.7 Conclusion
References
7: The Effects of Legal and Illegal Drugs on Placental Function
7.1 Introduction
7.2 Smoking During Pregnancy
7.2.1 Tobacco Ingredients
7.2.2 Effects on Placental Morphology
7.2.3 Effects on Trophoblast Cells
7.2.4 Oxidative Stress and Endothelial Dysfunction
7.2.5 Placental Transcriptome
7.3 Alcohol During Pregnancy
7.3.1 Effects on Placental Morphology
7.3.2 Effects on Trophoblast Cells
7.3.3 Oxidative Stress and Endothelial Dysfunction
7.4 Methamphetamines and MDMA
7.5 Cocaine
7.6 Opiates
7.6.1 Placental Transfer
7.6.2 Effects on Trophoblast Cells
7.7 Cannabis
7.7.1 Placental Transfer
7.7.2 Effects on Trophoblast Cells
References
8: Placenta-Related Hemorrhage: Pathophysiology, Diagnostics, Management
8.1 The Placenta Accreta Spectrum (PAS)
8.1.1 Introduction
8.1.2 Epidemiology
8.1.3 Risk Factors
8.1.4 Definition
8.1.5 Pathogenesis
8.1.6 Diagnosis
Ultrasound for the Diagnosis of PAS
Thinning or Absence of the Myometrium
Placental Protrusion
Focal Expophytic Excrescence
Loss of the Clear Zone
Abnormal Placental Lacunae
Urinary Bladder Disruption
Uterovesical Hypervascularity
Subplacental Hypervascularity
Bridging Vessels
Vessels Feeding the Placental Lacunae: Lacunae Feeder Vessels
Summary Ultrasound
MRI for the Diagnosis of PAS
Laboratory Tests
8.1.7 Management and Therapy
Possible Procedure in case of Antenatal Diagnosis
Antepartum Management
Surgical Procedures
Conservative Procedure
Possible Procedure in case of Intrapartum Diagnosis
8.2 Placenta Praevia
8.2.1 Terminology
8.2.2 Morbidity and Mortality
8.2.3 Etiology and Risk Factors
Special Case Placenta Praevia Accreta
8.2.4 Diagnostics and Management
Clinical Management
8.2.5 Operational Procedure
Emergency Situation
Placenta Praevia, Originating from the Posterior Wall
Placenta Praevia, Originating from the Anterior Wall
Atony Risk
8.2.6 Summary
8.3 Umbilical Cord Insertion, Variations and Vasa Praevia
8.3.1 Umbilical Cord Insertion, Velamentous Cord Insertion
8.3.2 Vasa Praevia
8.4 Premature Placental Abruption
8.4.1 Incidence and Risk Factors
8.4.2 Definition
8.4.3 Etiology
8.4.4 Clinical Signs
8.4.5 Instrumental Diagnostics
B-Mode Sonography
Doppler Sonography
Cardiotocography (CTG)
Magnetic Resonance Imaging (MRI) and Computed Tomography (CT)
8.4.6 Laboratory Diagnostics
Serum Markers in the First and Second Trimester
Kleihauer-Betke Test
Blood Count/Coagulation Diagnostics
8.4.7 Clinical Care/Management
8.4.8 Conclusion
8.5 Primary and Secondary Tumors of the Umbilical Cord and Placenta
8.5.1 Tumors of the Umbilical Cord
8.5.2 Tumors of the Placenta
Primary Non-trophoblastic Tumors of the Placenta
Teratomas
Chorangiomas, Fibromas and Chorangiocarcinoma
Leiomyomas, Endometrial Stromal Tumors, Deciduomas, Hepatocellular Adenomas
Intraplacental Heterotopias
Secondary Tumors of the Placenta
Maternal Tumors
Fetal Tumors
Primary Trophoblastic Tumors of the Placenta
References
References on Section 8.1
References on Section 8.2
References on Section 8.3
References on Section 8.4
References on Section 8.5
9: Placental Imaging
9.1 Sonographic Assessment of the Placenta in the Second and Third Trimester and Ultrasound/MRI Morphology of the Placenta
9.1.1 Introduction
9.1.2 Localization
Low-Lying Placenta
Placenta Praevia
Untypical Placental Location
9.1.3 Placenta Accreta Spectrum (PAS)
Imaging
9.1.4 Echogenicity
Placental Lacunae
Septal Decidual Cysts
Placental Cysts of the Surface
Echogenic Cystic Lesions (Placental Bed Infarction)
Placental Infarction
Placental Hematoma
Breus’ Mole
Jelly-like Placenta
Mesenchymal Dysplasia of the Placenta
9.1.5 Maturation of the Placenta
9.1.6 Size and Shape
Accessory Placenta (Placenta succenturiata)
Placenta circumvallata
Placenta membranacea/Placenta diffusa
9.1.7 Placental Biometry and Volumetry
Thick Placenta
Small Sized Placenta
Placental Abruption
9.1.8 Summary
9.2 Doppler Sonography/Functional Diagnostics
9.2.1 Placental Vascular System
Fetoplacental Hemodynamics
Uteroplacental Hemodynamics
Disorders of Utero- and Fetoplacental Blood Flow
Placental Function
Placental Blood Flow
Oxygenation and Placental Metabolism
References
Section 9.1
Section 9.2
10: Disorders of Early Pregnancy and Pregnancy Loss
10.1 Early Pregnancy and Its Disturbance
10.1.1 Diagnosis of Early Pregnancy
General Remarks
Laboratory Diagnostics
Human Chorionic Gonadotropin (hCG)
Additional Factors, Hormones and Screening Tests
Verification of Early Pregnancy by Means of Sonography
10.1.2 Pregnancy Loss
Definition and Epidemiology
Clinical Stages of the Abortion Process
Causes of Pregnancy Loss
Chromosomal Abnormalities in Pregnancy Tissue
Genetic Causes in the Parents
Uterine Anomalies
Congenital Uterine Anomalies
Acquired Uterine Anomalies
Infections
Stimulants and Pollutants
Endocrine Causes
Psychosocial Factors
10.2 Recurrent Pregnancy Loss
10.2.1 Introduction
10.2.2 Established Risk Factors
Endocrine Dysfunctions
Anatomical Malformations
Infections
Chromosomal Disorders
Psychological Factors
Hemostasiological Factors
Immunological Factors
10.2.3 Possible New Risk Factors
Chronic Endometritis
Peripheral and Uterine Killer Cells
References
11: Placental Insufficiency/Placenta-Associated Diseases
11.1 Placental Disorders: Pathophysiology
11.1.1 Introduction
11.1.2 Preeclampsia
Definition
Classification and Epidemiology
Long-Term Effects
Pathophysiology
Risk Factors for the Development of Preeclampsia
Differences Between Early and Late Onset Preeclampsia
Presentation and Falsification of the Outdated Hypothesis on the Etiology of Preeclampsia
Deficient Trophoblast Invasion and Preeclampsia
Deficient Placental Perfusion, Placental Hypoxia and Preeclampsia
What Is the Effect of the Funnel-Shaped Dilatation of the Uterine Arteries?
What Is the Effect of Deficient Trophoblast Invasion?
Does This Really Lead to Deficient Placental Perfusion and Placental Hypoxia?
Possible Explanation of the Etiology of Preeclampsia
11.2 FGR: Diagnostics and Management
11.2.1 Terminology and Definition
11.2.2 Epidemiology
11.2.3 Cause and Risk Factors
11.2.4 Fetal Compensation
11.2.5 Outcome of the Child
11.2.6 Diagnostics and Monitoring
Growth Dynamics
Head-Abdomen Discrepancy
Amniotic Fluid Volume
Biophysical Profile
Doppler Ultrasound
Umbilical Arteries and Descending Aorta
Middle Cerebral Artery and Cerebroplacental Ratio (CPR)
Ductus Venosus
11.2.7 Therapeutic Management–Delivery Indication
Growth Restriction Intervention Trial (GRIT)
Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT)
Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)
11.3 Preeclampsia: Diagnosis and Management
11.3.1 Definition and Classification
11.3.2 Causes and Risk Factors
11.3.3 Diagnosis and Early Detection
11.3.4 Biomarkers in Diagnostics and Prediction
11.3.5 Risk Assessment for Preeclampsia in the Context of First Trimester Screening and Secondary Prophylaxis
11.3.6 Clinical Management
11.3.7 Possible Future Therapeutic Approaches
11.3.8 Long-Term Morbidity
References
Section 11.1
Section 11.2
Section 11.3
12: The Placenta in Twins
12.1 Introduction
12.2 Structural Differences Between Monochorial and Dichorial Placentas
12.2.1 Chorionicity
12.2.2 Assessment of the Placenta in Early Pregnancy
12.2.3 Assessment of the Placenta in Late Pregnancy
12.2.4 Assessment of the Placenta after Delivery
12.3 The Placenta in Twin-to-Twin Transfusion Syndrome (TTTS)
12.3.1 Vascular Anastomoses in TTTS
12.3.2 Importance of the Umbilical Cord in TTTS
12.3.3 Unequal Division of the Placenta in TTTS
12.3.4 Significance of Other Placental Factors for TTTS
12.4 Monochorial Placenta and Discordant Growth
12.4.1 Unequal Division of the Placenta and Discordant Growth
12.4.2 Anastomoses and Discordant Growth
12.4.3 Umbilical Cord and Growth Discordance
12.4.4 Molecular Changes and Discordant Growth
12.4.5 Other Placental Factors and Discordant Growth
12.5 Dichorial Placenta and Discordant Growth
12.5.1 Umbilical Cord and Discordant Growth
12.5.2 Placental Pathology and Discordant Growth
12.6 Conclusion
References
13: Fetal Programming
13.1 Introduction
13.2 Between Hypothesis and Epidemiology
13.2.1 This Is How It All Began: The Barker Hypothesis and First Epidemiological Studies
13.2.2 Obesity, Insulin Resistance and Metabolic Syndrome
13.2.3 Cardiovascular Diseases
13.2.4 Altered Immune Response and Autoimmune Diseases
13.2.5 Memory and Psychiatric Disorders
13.2.6 Gender-specific Programming
13.3 Underlying Mechanisms
13.3.1 Direct Mother-to-Child Mediators
Maternal Hormones, Growth Factors and Cytokines
Hypothalamic-Pituitary-Adrenal (HPA) Axis
Signaling Pathways Via Placentally-expressed Growth Factors
Maternal Microchimerism
13.3.2 Epigenetic Changes
13.4 Examples of Exogenous Stimuli of Fetal Programming
13.4.1 Maternal Malnutrition and Placental Insufficiency
13.4.2 Maternal Oversupply and Gestational Diabetes
13.4.3 Glucocorticoid Administration for Lung Maturation Induction
13.5 Contradictions and Alternative Approaches
13.6 Pregnancy as an Option for Future Health Prevention
References
14: Fetal Cells and Cell-Free Nucleic Acids in Maternal Blood: Genetic and Immunological Aspects
14.1 Introduction
14.2 Fetal Cells and Fetal DNA in Maternal Blood: A Centuries-Old Phenomenon
14.3 Cell-Free DNA: Current Status for Non-invasive Prenatal Testing
14.3.1 Whole Genome Sequencing
14.3.2 Targeted Genome Sequencing
14.3.3 SNP Approach
14.3.4 Technical Principles of Currently Available Non-invasive Prenatal Tests
14.3.5 Clinical Use of NIPT, Its Limitations and Impact on Prenatal Care
14.4 Trophoblast Cells in the Cervix – Diagnostic Use and Insight into Fetomaternal Pathologies
14.5 Placental Cell-Free DNA: An Activator of the Maternal Immune System and Initiator of Birth?
14.6 MicroRNA from the Placenta: New Antiviral Agents?
14.7 Circulating Fetal Cells: Their Role in Pregnancy-Associated and Postpartum Diseases
14.8 Conclusions
References
15: Research Aspects and In Vitro Models
15.1 Trophoblast Cell Culture Models
15.1.1 Primary Trophoblasts
15.1.2 Trophoblast Cell Lines
Choriocarcinoma Cell Lines
Trophoblast Hybridoma Cells
Transformed Trophoblasts
15.2 Placental Explant Cultures
15.3 Endothelial Cells
15.3.1 Human Umbilical Vein Endothelial Cells (HUVECs)
15.3.2 Primary Placental Endothelial Cells
15.4 Placental Macrophages
15.4.1 Decidual Macrophages
15.4.2 Hofbauer Cells
15.5 Placenta Ex Vivo Perfusion
15.5.1 Methodology
15.5.2 Applications in Research
References
16: Maternal Disease Affecting the Placenta: Diabetes Mellitus
16.1 Definition and Epidemiology
16.1.1 Definition
16.1.2 Epidemiology
16.2 Effects of Hyperglycemia in Pregnancy
16.3 Diagnosis and Therapy
16.3.1 Screening and Diagnosis of Gestational Diabetes
16.3.2 Therapy
16.3.3 Timing of Delivery in Patients with Diabetes
16.4 Significance of the Placenta for Glucose Metabolism in Pregnancy
16.5 Placental Changes in Patients with Diabetes
16.5.1 Placental Changes in Pre-Existing Diabetes
16.5.2 Placental Changes in Gestational Diabetes
16.6 Placental Histology in Diabetes—Consequences of a Histopathological Reprocessing?
References
Index