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The Guide to Investigation of Mouse Pregnancy is the first publication to cover the mouse placenta or the angiogenic tree the mother develops to support the placenta. This much… Read more
LIMITED OFFER
Immediately download your ebook while waiting for your print delivery. No promo code needed.
The Guide to Investigation of Mouse Pregnancy is the first publication to cover the mouse placenta or the angiogenic tree the mother develops to support the placenta. This much-needed resource covers monitoring of the cardiovascular system, gestational programming of chronic adult disease, epigenetic regulation, gene imprinting, and stem cells.
Offering detailed and integrated information on how drugs, biologics, stress, and manipulations impact pregnancy in the mouse model, this reference highlights techniques used to analyze mouse pregnancy. Joining the ranks of much referenced mouse resources, The Guide to Investigation of Mouse Pregnancy is the only manual providing needed content on pregnancy in animal models for translational medicine and research.
This book is intended for basic scientists and clinical investigators researching reproduction, immunology, developmental biology, cardiology, gynecology, animal care, and veterinary medicine; graduate students; postdocs; veterinary technologists; and laboratory technologists.
Biographies
Preface
Conception of This Publication
Goals
The Many Thank Yous Over the Course of This Project
Contributors
Part I: Atlas
1. The Cycling and Pregnant Mouse: Gross Anatomy
Chapter Summary
Abbreviations
Introduction
Anatomic Changes in the Appearance of the Cycling and Pregnant Uterus
Death of a Conceptus Does not Mean Pregnancy Failure
Postpartum Uterine Involution
Illustrative Plates
References
2. Implant Site Dissections
Chapter Summary
Abbreviations
Introduction
Dissection of Gestation Day 6.5–9.5 Uteri and Implant Sites
Collection of the MLAp
Dissection of Uteri and Implant Sites between Gestation Day 10.5 and Term
Illustrative Plates
References
3. Microscopic Anatomy of the Pregnant Mouse Uterus Throughout Gestation
Chapter Summary
Abbreviations
Introduction
4. Anatomy of the Mouse Placenta Throughout Gestation
Chapter Summary
Abbreviations
5. Whole-Mount Immunohistochemistry of Early Implantation Sites
Chapter Summary
Abbreviations
Introduction
Benefits and Limitations
Whole-Mount Atlas Plates
References
6. Magnetic Resonance Imaging of the Mouse Placenta
Chapter Summary
Introduction
Methods
Future Perspectives
References
Part II: Basic Biology
Interval A. Estrus, Early Development, Implantation and Uterine Receptivity
7. Reproductive Tract Changes During the Mouse Estrous Cycle
Chapter Summary
Acknowledgments
Introduction
Female Mouse Reproductive Tract Anatomy
The Mouse Estrous Cycle
References
8. First Cell Fate Decisions in Early Development: Towards Establishment of the Trophoblast Lineage
Chapter Summary
Abbreviations
Introduction
Cell Fate Decisions in Early Development
Transcription Factors Regulating Early Cell Fate Decisions
Epigenetic Modifications Underpin the Establishment of Stably Committed Cell Lineages
Stem Cells to Model the First Cell Lineages: Deconstructing the Early Embryo
Trophoblast Stem Cells as Critical Tool to Study Placental Development
References
9. Tetraploid Complementation Assay
Chapter Summary
Abbreviations
Review
References
10. Biology of the Ectoplacental Cone
Chapter Summary
Abbreviations
Chapter Contents
The Blastocyst at the Uterine Cavity: Preparing for Embryo Implantation
Embryo Implantation and the Mural Trophoblast
Growth Characteristics and Fate of the Ectoplacental Cone Cells
Summary
References
11. Decidualization and Endometrial Extracellular Matrix Remodeling
Chapter Summary
Abbreviations
Establishment of the Maternal–Fetal Interface
Endometrial Compartmentalization
Endometrial Modifications Preceding Decidualization
Decidualization of the Endometrium
Dynamics of Decidual Development
Control of Decidualization
Mesenchymal and Epithelial Aspects in Decidualization
Endometrial Extracellular Matrix Remodeling
Regulation of Endometrial ECM Remodeling
References
Interval B. The Maternal-Fetal Interface - Primitive Streak to Term
12. Postimplantation Development of the Chorioallantoic Placenta
Chapter Summary
Abbreviations
Morphology of the Chorioallantoic Placenta
Morphogenesis of the P-TGC Layer and Junctional Zone
Morphogenesis of the Labyrinth Zone
Studying Placental Phenotypes
References
13. Unique Features of Endometrial Dynamics During Pregnancy
Chapter Summary
Abbreviations
Overview
Pregnancy-Associated Uterine Tissue Remodeling
Luminal Epithelium: Receptivity, Regression and Restoration
Biology of the Endometrial Stroma
References
14. Pathology Analysis of the Placenta
Chapter Summary
Abbreviations
Considerations in the Structural Analysis of Mouse Placental Specimens
Major Lesion Patterns in Mouse Placenta and Their Causes
References
15. Changes in Structures and Relationships of Trophoblasts, Leukocytes, and Maternal Vessels in Implantation Sites to Midpregnancy
Chapter Summary
Abbreviations
Introduction
Orientation Landmarks: Features of the Uterine Wall Visualized by Whole Mount In Situ Immunohistochemistry
Whole-Mount Features of Gd 4.5–5.5 Implant Sites
Whole-Mount Features of Gd 6.5–9.5 Implant Sites
Roles of Decidual Lymphocytes Defined by Whole-Mount Studies
Whole-Mount Definition of Implant Site Relationships in Mice Lacking NK Cell Activation Receptors
Whole-Mount Identification of Changes in Implant Sites in Mice Genetically Ablated for PGF
Summary and Future Perspectives
References
16. The Uteroplacental, Fetoplacental, and Yolk Sac Circulations in the Mouse
Chapter Summary
Abbreviations
Introduction
The Yolk Sac Circulation
The Uteroplacental Circulation
The Umbilical Cord and Fetoplacental Circulation
Strain Differences in Placental Circulation
Summary and Future Perspectives
References
17. Physiological Exchange across Mouse Placenta
Chapter Summary
Abbreviations
Introduction
Flow and Membrane Limited Transfer
Transporter Mediated Transfer
Endocytosis/Exocytosis
Summary and Future Perspectives
References
Further Reading
18. Hypoxia-Associated Regulation within Implantation Sites
Chapter Summary
Abbreviations
Introduction
Oxygen and Pregnancy
Hypoxia-Inducible Factors
Gene Knockout Models
High-Altitude Pregnancies
Hypoxic Chambers
Pharmacological Models
Surgical Models
Summary and Future Perspectives
References
19. Leukocyte Population Dynamics and Functions at the Maternal–Fetal Interface
Chapter Summary
Abbreviations
Acknowledgments
Introduction
General Considerations
NK Cells
Macrophages
Dendritic Cells
Monocytes and Other Myeloid Precursors
T Cells
Summary and Future Perspectives
References
20. In Vivo Tracking of Mononuclear Cells in the Virgin Uterus and in Implantation Sites
Chapter Summary
Abbreviations
Acknowledgments
Introduction
Two-Photon Microscopy and Its Use in Immunology
Intravital Imaging of Uterus and Placentas
Advantages and Limits of New Uterus/Placenta Intravital Imaging Techniques
Image Processing
Concluding Remarks about Intravital Imaging of Uterus and Placenta
References
21. Microchimerism in Mouse Pregnancy
Chapter Summary
Abbreviations
Introduction to Microchimerism
Fetal Microchimerism
Conclusion and Perspectives
References
22. Systems Biology Analyses of the Placenta
Chapter Summary
What is Systems Biology?
Genome Wide vs Targeted Techniques
Measuring Gene Expression
Sample Generation
Software
Statistics
Bioinformatics
Examples
Conclusion
References
23. Contribution of Placental Genomic Imprinting and Identification of Imprinted Genes
Chapter Summary
Genomic Imprinting: Lessons from Mice
Why Imprinting?
Imprinting in the Placenta: A Special Role?
Concluding Remarks
References
24. Epigenetics of Placental Development and Function
Chapter Summary
Abbreviations
Introduction
The Use of Epigenetics and Epigenomics to Describe Mammalian Cells and Tissues
DNA Methylation
Histone Modifications
Epigenetic Control of Placental Development and Functions
Epigenetic Abnormality in Developmental Defects and Chronic Diseases: The Influence of Drug and Environmental Chemicals and Nutrition on Epigenetic Systems
Evolutionary Aspects of Placenta Viewed through Epigenetics
Summary and Future Perspectives
References
25. Genome-Wide Analysis of the Mouse Deciduoma
Chapter Summary
Abbreviations
Introduction
Mouse Deciduoma Models: Historical and Current Perspectives
Importance of Choosing a Suitable Model and Sample Type
Transcriptome Analysis Using Microarrays
New Frontiers in Genome-Wide Analyses of Mouse Deciduoma
Perspectives on Future Genome-Wide Deciduoma Research
References
26. Conditional Gene Deletion in the Placenta Using the Cre-loxP System
Chapter Summary
Abbreviations
Overview
Validation of Cre-loxP Conditional Gene Deletion Mouse Models
Summary
References
27. Genetic Engineering of Mice to Investigate Uterine Function in Early Pregnancy
Chapter Summary
Abbreviations
Introduction
Transgenic Models to Assess Uterine Function
Use of Homologous Recombination and Targeting in ES Cells to Generate Efficient Models to Elucidate Uterine Function
Summary
References
28. Lentivirus-Mediated Transduction of Optical Reporter Genes in Blastocysts for Placental Studies
Chapter Summary
Abbreviations
Acknowledgment
Introduction
Modulation of Placental Functions by Generation of Chimeric Placentas
Placental Gene Manipulation Based on Trophoblast Lineage-Specific Promoters
Virus-Mediated Placenta-Specific Gene Delivery
Summary and Future Perspectives
References
29. Blood Pressure Regulation during Mouse Pregnancy
Chapter Summary
Abbreviations
Introduction
Cardiovascular Changes in Mammalian Pregnancy (Human vs Mouse)
Choices between Blood Pressure Recording Methodologies
Normal Mouse Pregnancy
Hypertensive Mouse Models
Other Experimental Models Involving Reproduction
Advantages and Limitations of Radiotelemetry
References
30. Intravital Imaging of Vasoactivity in the Uterine Arterial Tree during Pregnancy
Chapter Summary
Abbreviations
Introduction
Blood Flow Control
Intravital Microscopy Preparation
Imaging of the Endometrial Vasculature
Branch Order Classification of the Endometrial Vasculature
Vascular Reactivity of Intravital Preparation
Summary and Future Perspectives
References
31. Multimodal Imaging of the Mouse Placenta
Chapter Summary
Abbreviations
Acknowledgments
Introduction
Ultrasound Imaging of the Mouse Placenta
Intravital Fluorescence Microscopy of the Mouse Placenta
Photoacoustic Imaging of the Mouse Placenta
Utilizing Bioluminescence Reporter Genes for Placenta Imaging (Luciferin–Luciferase)
MRI Imaging of the Mouse Placenta
Future Perspectives
References
Interval C. Parturition, Lactation and Postnatal Outcomes
32. Regulation of Parturition
Chapter Summary
Uterine Activation during Labor
Myometrial Stimulation
Physiologic Uterine Inflammation and Labor Onset
The Problem of Preterm Birth
Mouse Models of PTB
Genetic Manipulation of Labor Pathway in the Mouse
Prevention of PTB
Conclusions
References
33. Cervical Changes Accompanying Birth
Chapter Summary
Abbreviations
Acknowledgments
Introduction to the Pregnant Cervix
Anatomy and Histology of the Mouse Cervix
ECM Components of the Pregnant Cervix
Phases of Cervical Remodeling
Premature Cervical Ripening in Preterm Birth
Summary and Future Perspectives
References
34. Peri-Partum Changes to Mouse Pubic Symphysis
Chapter Summary
Abbreviations
Acknowledgments
Introduction
Nongravid Pubic Symphysis
Phases of PS Remodeling
Relevance of Postpartum PS Recovery
Conclusions
References
35. Mammary Gland Morphogenesis and Function during Pregnancy
Chapter Summary
Abbreviations
Introduction
Mammary Gland Structure
Postnatal Mammary Gland Development
The Intersection of Progesterone and Prolactin Signals Specifies Mammary Epithelial Proliferation and Differentiation during Pregnancy Progression
Summary and Future Perspectives
References
36. Gestational Programming of the Cardiovascular System
Chapter Summary
Abbreviations
Introduction
Hemodynamic and Biochemical Origins of Cardiovascular Disease
Embryonic and Fetal Cardiac Assessments
3D Cardiac Imaging
Assessment of Cardiac Performance Using Ultrasound Biomicroscopy In Utero
Concluding Remarks
References
37. Maternal Stress-Mediated Gene Expression Changes in the Mouse Placenta: A Mosaic Hypothesis of Epigenesis
Chapter Summary
Abbreviations
Acknowledgment
Introduction
What is the Role of Epigenetics in Stress-Induced and Other Placental Gene Expression?
To What Extent is Murine Placental Gene Expression Altered during the Course of Gestation?
To What Extent is Placental Gene Expression Altered by Maternal Protein/Caloric Deprivation?
What are the Correlates of Dietary Deprivation in Placentas of Other Mammals?
To What Extent is Placental Gene Expression Altered by Maternal Caloric Excess?
To What Extent is Placental Gene Expression Altered by Maternal Hypoxia?
What are the Correlates in the Human Placenta?
What are the Overall Perspectives and Critical Questions to Explore?
Summary
References
38. Pregnancy Alterations from Environmental Pollutants
Chapter Summary
Abbreviations
Introduction
Reproductive and Developmental Toxicity Testing
Environmental Air Pollution
Reproductive Toxicity of Air Pollution
Conclusions
References
Part III: Protocols
39. Monitoring Mouse Estrous Cycles
Chapter Summary
Protocol: Collecting the Vaginal Epithelial Cells
Protocol: Staining Vaginal Smears with May-Grünwald Giemsa stain
References
40. Lentivirus Transduction of Gene Tags in Blastocysts
Chapter Summary
Abbreviations
Acknowledgment
Overview
Protocol
Major Technical Limitations
Troubleshooting
References
41. Tetraploid Complementation Assay
Chapter Summary
Abbreviations
Protocol
Materials
Reagents
Method
References
42. Pseudopregnant Bead-Induced Mouse Deciduoma Model
Chapter Summary
Abbreviations
Overview
Materials
Solutions
Protocol
Alternate Proven Ways to Do Bead Transfer
References
43. Ectoplacental Cone Isolation, Culture and Assessment
Chapter Summary
Abbreviations
Culturing Blastocysts to Study Trophoblast Cells
Isolation and Culture of Ectoplacental Cone
Coculture Systems
The Ectoplacental Cone as a Xenograft
Summary and Perspectives
References
44. Layer-Enriched Tissue Dissection of the Mouse Placenta in Late Gestation
Chapter Summary
Abbreviations
Overview
Protocol
References
45. Protocols for Placental Histology
Chapter Summary
Processing Sequence for Mouse Placental Specimens
Histotechnological Practices for Preparing Mouse Placenta
Final Thoughts
References
46. Best Practice for Quantifying the Microscopic Structure of Mouse Placenta: The Stereological Approach
Chapter Summary
Abbreviations
Overview
Protocol
Concluding Remarks
References
47. Electron Microscopy and Immunoelectromicroscopy Protocols
Chapter Summary
Abbreviations
Overview of Microscope Images
The Physics of Electrons and the Chemistry of Biological Molecules in Electron Microscopy
Handling of Mouse Reproductive Organs for Ultrastructural Analyses
Protocols for Sample Processing for TEM Ultrastructural and Immunocytochemical Analyses
Further Reading
48. Laser Capture Microdissection
Chapter Summary
Abbreviations
Introduction
Advantages of LCM
Disadvantages of LCM
LCM Procedure
Sample Preparation for LCM
Slide Preparation
Staining
Microdissection Procedure
RNA Extraction
Antisense RNA Amplification (Optional)
cDNA Synthesis
Tips for Good Sample Processing
Important Precautions while Dealing with RNA
Common Problems Encountered in LCM
References
49. Immunofluorescence and Immunohistochemistry
Chapter Summary
Abbreviations
Overview
Protocol
Troubleshooting
Double Staining
Reference
50. Nonradioactive In Situ Hybridization: Optimization for Tissue Sections from Pregnant Uteri and Placenta during the First Half of Pregnancy
Chapter Summary
Abbreviations
Overview
Probe Preparation
Tissue and Slide Preparation
Hybridization
Posthybridization Wash
Color Development
Fluorescent In Situ Hybridization
Potential Optimization Steps
Kits, Reagents, and Recipes
References
51. Whole Mount In Situ Immunohistochemistry
Chapter Summary
Abbreviations
Overview
Protocol
Orientation of Stained Specimens
Technical Limitations
References
52. Guidelines for Evaluation of Reproductive and Developmental Endpoints
Chapter Summary
Abbreviations
Overview
Initial Considerations
Study Protocol
Reporting
References
53. Flow Cytometric Analysis of Myometrial and Decidual Cell Suspensions
Chapter Summary
Abbreviations
Overview
Protocol
Subset Analysis
Technical Limitations
References
54. Uterine Leukocyte Isolation and Culture
Chapter Summary
Abbreviations
Overview
Uterine Leukocyte Isolation
Uterine Leukocyte Culture
Protocols
References
55. Scanning Electron Microscopy and Micro-Computed Tomography Imaging of the Utero- and Fetoplacental Circulations
Chapter Summary
Abbreviations
Acknowledgments
Overview
Perfusion and Casting of the Uteroplacental Vascular Tree
Perfusion and Casting of the Fetoplacental Vascular Tree
Scanning Electron Microscope Imaging
Micro-Computed Tomography Imaging
References
56. Radiotelemetry in Mouse Pregnacy
Chapter Summary
Abbreviations
Overview
Required/Suggested Equipment
Surgical Protocol
Postoperative Care
Data Acquisition and Analysis
Summary
References
57. Ex vivo Perfusion of the Mouse Placenta for Maternal–Fetal Interaction Studies during Pregnancy
Chapter Summary
Abbreviations
Acknowledgments
Overview
Equipment and Reagents
Protocol
Critical Steps
Anticipated Results
References
58. Evaluation of Placental Transport Function
Chapter Summary
Abbreviations
Isolated Mouse Placental Plasma Membrane Vesicles
Mouse Placental Fragments
Measurement of Unidirectional Maternofetal Solute Clearance across the Intact Mouse Placenta
Advantages, Limitations, and Technical Challenges of These Procedures
References
59. Hypoxia-Associated Regulation within Implantation Sites
Chapter Summary
Abbreviations
Overview
Fiber-Optic Oxygen Microsensor
Conclusions
References
60. Method to Locate the Uterine Artery in Mice for Micro-Ultrasound Doppler Blood Velocity Examination
Chapter Summary
Abbreviations
Overview
Protocol
References
61. Two-Photon Intravital Microscopy of the Virgin and Pregnant Mouse Uterus
Chapter Summary
Abbreviations
Overview
Protocols
Final Considerations about These Techniques
References
62. Intravital Imaging of Vasoactivity in the Uterine Arterial Vasculature Tree during Pregnancy
Chapter Summary
Abbreviations
Overview
Protocol
Tissue Orientation
Technical Limitations
References
63. MRI, Intra-vital, and Ex-vivo Fluorescence Microscopy of the Mouse Uterine Vasculature and Placenta
Chapter Summary
Abbreviations
Acknowledgment
Overview
Magnetic Resonance Imaging
Optical Imaging
References
64. Assessment of Changes in the Peripartum Cervix
Chapter Summary
Abbreviations
Acknowledgments
Assessment of Cervical Collagen Structure by Second-Harmonic Generation
Analysis of Cervical Glycosaminoglycans
Identification and Quantification of Immune Cell Populations by Flow Cytometry
Preterm Birth Mouse Models
References
65. Pubic Symphysis Evaluation
Chapter Summary
Abbreviations
Acknowledgments
Introduction
Animals and Interpubic Tissue Collection
Classical Histological Fixation and Embedding
Classical Histological Staining
Morphometric Determination of the Length Profiles of Elastic Fibers
Hyaluronic Acid Histochemical Analysis with Hyaluronic Acid Probes
TUNEL Analysis for Evaluation of Cell Death in Interpubic Tissue
Immunohistochemical/Immunofluorescence Protocols for Interpubic Tissues
Transmission Electron Microscopy
Scanning Electron Microscopy
Explant Culture of Interpubic Tissues
Biochemical and Molecular Processing
Conclusion
References
66. Labor and Preterm Labor
Chapter Summary
Abbreviations
Monitoring of Labor and Delivery
Detection of Term and Preterm Parturition
67. Epithelial Transplantation into the Cleared Mammary Fat Pad
Chapter Summary
Abbreviations
Overview
Protocol
Technical Problems and Limitations
References
68. Dietary and Hypoxic Protocols That Alter Placental Gene Expression in Response to Maternal Stress
Animals, Breeding, and Tissue Collection
Antenatal Maternal Protein Restriction
Antenatal Maternal Caloric Excess
Antenatal Maternal Hypoxia
Biological Significance
References
69. Parental-Specific Gene Expression and Epigenetic Analyses of Imprinted Genes in Mouse Placenta
Chapter Summary
Abbreviations
Overview
Protocol
Technical Limitations
References
70. A Method for Obtaining Epigenomic Data
Chapter Summary
Bisulfite Reaction
Chromatin Immunoprecipitation
Bioinformatics Tools for Genome-wide Studies
References
71. Methods for Genetic Engineering in Mice
Chapter Summary
Abbreviations
Overview
Germline Gene Ablation Targeting Vector
Conditional Gene Ablation Targeting Vector
Conditional Overexpression Targeting Vector
ES Cell Targeting
Picking ES Cell Colonies and Injection Preparation
Generation of Chimeric Mice
Identification of Genetically Engineered Mice
Equipment
Reagents
Summary and Future Perspectives
References
Appendix. Reproductive Parameters of Common, Commercially Available Mouse Strains
Index
BC
AY
FD
SA