Cellular and Molecular Aspects of Implantation

Long was I hugg'd close-long and long. Immense have been the preparations for me, Faithful and friendly the arms that have help'd me. Cycles ferried my cradle, rowing and rowing like friendly boatmen. For room to me stars kept aside in their own rings, They sent influences to look after what was to hold me. Before I was born out of my mother, generations guided me, My embryo has never been torpid, nothing could overlay it. -Walt Whitman, "Song of Myself" The womb is the seat of all mammalian life. In pregnancy, the uterus acquires this impor- tance with the arrival of the fertilized egg, which takes up residence for periods ranging from about 2 weeks in the opossum to about 2 years in the elephant. The arrival of the embryo signals a crucial time for the establishment of pregnancy. For several days the blas- tocyst remains free in the uterine lumen, where it depends on uterine secretions for its sur- vival and differentiation. During this time, essential changes in the endometrium take place in preparation for attachment of the blastocyst and implantation. Early embryonic loss is an economic problem of global proportions in animal husbandry, where, in pigs and cattle for example, some 30% of all fertilizations fail to result in a pregnancy. In humans this figure may be even higher, and estimates of early spontaneous abortions range from 40 to 60% of all conceptions.

Table of Contents:
I: Perspectives.- 1 Viviparity.- I. Introduction.- II. Viviparity as a Reproductive Mechanism.- III. Adaptations for Ovoviviparity and Viviparity in Invertebrates.- IV. Adaptations for Viviparity in Fishes.- A. Elasmobranchs.- B. Teleosts.- C. Latimeria: The Living Coelacanth.- V. Amphibian Viviparity.- VI. Reptilian Viviparity.- VII. Adaptations for Viviparity in Mammals.- A. Monotremes (Prototheria).- B. Marsupials (Metatheria).- C. Eutheria.- VIII. The Corpus Luteum and the Establishment of Pregnancy.- IX. The Maternal Recognition of Pregnancy.- X. Immunological Transactions in Early Pregnancy.- References.- 2 My Life with Mammalian Eggs.- I. Introduction.- II. In Vitro Fertilization of Mammalian Eggs.- III. Storage and Transfer of Eggs.- IV. Interspecific Fertilization and Egg Transfer.- V. Effects of Steroids and Other Compounds on the Transportation and Development of Eggs.- VI Summary.- References.- II: Cell Biology of the Developing Egg.- 3 The Origin of Trophoblast and Its Role in Implantation.- I. Introduction.- II. The Trophectoderm Cell Lineage.- A. What Is Trophoblast?.- B. How and When Is the Trophectoderm Cell Lineage Established?.- III. The Role of the Trophectoderm Cell Lineage in Implantation.- A. Uterus-Trophectoderm-ICM Interactions.- B. Species Specificity of the Trophoblast-Uterine Interaction.- IV. Conclusions.- Discussion.- References.- 4 The Generation and Recognition of Positional Information in the Preimplantation Mouse Embryo.- I. Introduction.- II. Asymmetries in the Oocyte.- III. Asymmetries at Fertilization.- IV. Asynmietries in Cleavage.- V. Compaction.- A. Description of Compaction.- B. Control of Compaction.- C. Consequences of Compaction for Blastocyst Formation.- 1. Cytochalasin D Treatment.- 2. Treatment with Antiserum to Embryonal Carcinoma Cells.- D. Mechanisms by Which Compaction Might Generate Positional Information during Blastocyst Formation.- VI. Summary and Conclusions.- Discussion.- References.- 5 Relationship between the Programs for Implantation and Trophoblast Differentiation.- I. Introduction.- II. What Is the Nature of Blastocyst Factors Involved in Implantation?.- III. What Is the Relationship between Implantation and Other Differentiative Events?.- IV. When Are Implantation-Related Gene Products Produced?.- V. Conclusions and Speculations.- Discussion.- References.- 6 Cellular and Genetic Analysis of Mouse Blastocyst Development.- I.Introduction.- II. Cell Determination during Early Mouse Embryogenesis.- A. Cell Determination in the Inner Cell Mass.- B. Cell Determination in the Primary Ectoderm.- III. Mutations at the a Locus Affecting Implantation.- A. Genetics.- B. Embryology.- 1. Histological Observations.- 2. Ultrastructural Observations.- 3. Experimental Observations.- IV. Conclusions.- Discussion.- References.- III: Macromolecular Synthesis in the Developing Egg.- 7 Mobilization of Genetic Information in the Early Rabbit Trophoblast.- I. Introduction.- II. Results and Discussion.- A. Unique-Sequence DNA Transcription.- B. Polysome Assembly and Ternary Complex Formation.- C. Cytoplasmic DNA.- D. RNA-Directed DNA Polymerase.- III. Summary.- Discussion.- References.- 8 Activity of RNA and DNA Polymerases in Delayed-Implanting Mouse Embryos.- I. Introduction.- II. Materials and Methods.- A. Preparation of Embryo Donors.- B. Radiolabeling of Embryos for the Determination of RNA Polymerase Activity.- C. Specific Activity of the [3H]-UTP Pools.- D. DNA Polymerase Assay.- E. Analysis of Data.- III. Results.- A. Specific Activities of the [3H]-UTP Pools.- B. Rate of Incorporation of [3H]Uridine into RNA.- C. RNA Polymerase Activity.- D. DNA Polymerase Activity.- IV. Summary.- Discussion.- References.- 9 A Reexamination of Messenger RNA Populations in the Preimplantation Mouse Embryo.- I. Introduction.- II. Materials and Methods.- III. Results and Discussion.- A. mRNA in the Morula-Blastocyst Transition Period.- B. Stable mRNA and Posttranscriptional Control in Early Cleavage.- C. Inhibition of Translation with Cap Analogs.- D. End-Labeling of Embryo RNA.- E. Qualitative Analysis of End-Labeled RNA.- IV. Concluding Remarks.- Discussion.- References.- 10 Intrinsic and Extrinsic Patterns of Molecular Differentiation during Oogenesis, Embryogenesis, and Organogenesis in Mammals.- I. Introduction.- II. Translational Patterns of Oocytes Undergoing Resumed Meiosis.- III. Translational Patterns of Preimplantation Embryos.- A. Support of Early Embryogenesis by Oocyte Components.- B. Differential Protein Synthesis at the Blastomere Level.- IV. Translational Patterns of Blastocysts during Activation from Facultative Delayed Implantation.- V. Translational Patterns during Limb Organogenesis.- Discussion.- References.- IV: Uterine Preparation for Implantation.- 11 Cell Proliferation and Cell Death in the Endometrium.- I. Introduction.- II. Assessment of Cell Death.- III. Results.- IV. Conclusions.- Discussion.- References.- 12 Shifts in Uterine Stromal Cell Populations during Pregnancy and Regression.- I. Introduction.- II. Involvement of the Uterine Fibroblast and Monocyte-Macrophage in Modeling of the Extracellular Matrix.- III. Transient Invasion of Blood Leukocytes into the Rat Uterine Stroma in the Peripartum Period (Day 16 Gestation through Day 3 Postpartum).- IV. Experimental Analysis of Cellular Aspects of Peripartum Uterine Differentiation.- V. Cellular Evidence Related to the Postulated Immunosuppressant Action of Progesterone.- Discussion.- References.- 13 Separated Cell Types as Analytical Tools in the Study of Decidualization and Implantation.- I. Historical Perspective.- II. Cell Separation Techniques.- A. Method for Separating Individual Cell Types from the Rat Uterus.- 1. Epithelial Cells,.- 2. Stromal Cells.- 3. Myometrial Cells.- 4. Viability and Yield.- III. Estrogen Receptor Assays.- A. Estrogen Receptor in Individual Cell Types from Immature Rat Uterus.- B. Comparison with Data from Whole Immature Rat Uterus.- C. Estrogen Receptors in the Preimplantation Uterus.- D. Estrogen Receptors in Individual Cell Types from the Preimplantation Uterus.- IV. Culture of Monolayers of Individual Uterine Cell Types.- V. Coculture of Blastocysts with Monolayers of Specific Uterine Cell Types.- Discussion.- References.- 14 Decidual Cell Function: Role of Steroid Hormones and Their Receptors.- I. Introduction.- II. Induction of Pseudopregnancy and Decidualization.- III. Estrogen Receptors in Decidual Tissue.- IV. Progesterone Receptors in Decidual Tissue.- V. Nuclear Receptors.- VI. Hormonal Control of Decidualization.- Discussion.- References.- V: Gene Expression in the Uterus.- 15 Mechanisms of Induction of Uterine Protein Synthesis: Hormonal Regulation of Uteroglobin.- I. Introduction.- II. Secretion of Uteroglobin.- III.Synthesis of Uteroglobin.- IV. Activity of Uteroglobin mRNA and Levels of Nuclear Progesterone Receptor.- Discussion.- References.- 16 Regulation of the Levels of mRNA for Glucose-6-phosphate Dehydrogenase and Its Rate of Translation in the Uterus by Estradiol.- I. Introduction.- II. Regulation of Uterine G6PD Synthesis by Estradiol.- III. Regulation of Uterine G6PD mRNA Levels by Estradiol.- IV. Regulation of Uterine G6PD Translation Time by Estradiol.- V. Regulation of the Rate of Processing of Uterine Pre-G6PD by Estradiol.- VI. Conclusions.- Discussion.- References.- 17 Uterine DNA Polymerase: Acquisition of Responsiveness to Estrogen during Postnatal Development of the Rat.- I. Introduction.- II. DNA Synthesis.- III. DNA Polymerase.- IV. Summary and Conclusions.- Discussion.- References.- 18 The Artificially Stimulated Decidual Cell Reaction in the Mouse Uterus: Studies of RNA Polymerases and Histone Modifications.- I. The Artificially Stimulated Decidual Cell Reaction as a Model for Studying Implantation.- II. The Biochemistry of the Decidual Cell Reaction.- III. RNA Metabolism.- IV. RNA Polymerases.- V. Histone Modifications.- VI. Template Activity.- VII. Summary.- Discussion.- References.- VI: Blastocyst-Uterine Interactions.- 19 Embryonic Signals and Maternal Recognition.- I. Introduction.- II. Embryonic Signals.- III. Onset of Trophoblast Estrogen Synthesis.- IV. Endogenous Precursors of Trophoblast Estrogens.- V. Mechanism of Action of Trophoblast Estrogens.- VI. Species Differences.- VII. Two-Way Interaction.- Discussion.- References.- 20 Uterine Blastotoxic Factors.- I. Introduction.- II. The Uterine State of “Nonreceptivity”.- III. Evidence for the Existence of a Blastotoxic Substance.- IV. The Effective Substance.- Discussion.- References.- 21 Lysosomal Mechanisms in Blastocyst Implantation and Early Decidualization.- I. Introduction.- II. Lysosomal Activity during Early Pregnancy.- III. Lysosomes and Epithelial Penetration.- IV. Lysosomes and Early Decidualization.- V. Summary.- Discussion.- References.- VII: Mechanisms of Implantation.- 22 The Role of Prostaglandins in Endometrial Vascular Changes at Implantation.- I. Introduction.- II. Changes in Endometrial Vascular Permeability in Response to Blastocysts.- III. Changes in Endometrial Vascular Permeability in Response to Artificial Stimuli.- IV. Timing of Uterine Sensitivity.- V. Which Prostaglandin(s)?.- VI. Source of Prostaglandins.- VII. Mode of Action of Prostaglandins.- VIII. Summary and Conclusions.- Discussion.- References.- 23 Comparison of Implantation in Utero and in Vitro.- I. Introduction.- II. Comparison of Development.- A. Hatching.- B. Adhesion Stage.- C. Outgrowth.- D. Outgrowth and Monolayers.- III. Analysis of Outgrowth.- IV. Prospects and Problems.- Discussion.- References.- 24 Time-Lapse Cinematography of Mouse Embryo Development from Blastocyst to Early Somite Stage.- I. In Vitro Development of Mouse Embryos from Blastocyst to Early Somite Stage.- II. In Vitro Monozygotic Twin Formation in Mouse Embryos.- III. Embryo Growth and Differentiation Factors in Embryonic Sera.- References.- VIII: Short Communications.- 1. The Effects of Estradiol-17 ? and Progesterone on the Volume of Uterine Fluid in Ovariectomized Mice.- 2. Presence of hCG-like Material in the Preimplantation Rabbit Blastocyst.- 3. Electron Microscopic Study of Rat ? Mouse Chimeric Blastocysts Produced by Embryo Aggregation.- 4. Characteristics of an Endogenous Inhibitor of Progesterone Binding in Rat Trophoblast.- 5. Histone Synthesis in Preimplantation Mouse Embryos.- 6. Use of Concanavalin A to Monitor Changes in Glycoprotein Synthesis during Early Mouse Development.- 7 The Role of Glycoproteins in the Development of Preimplantation Mouse Embryos.- 8. The Role of Blastolemmase in Implantation Initiation in the Rabbit.- 9. Estradiol-17 ? Dehydrogenase in Rat Endometrium at the Time of Implantation.- 10. The Pig Uterus Secretes a Progesterone-Induced Inhibitor of Plasminogen Activator.- 11. Role of a Uterine Endopeptidase in the Implantation Process of the Rat.- 12. The Role of Prostaglandins and Cyclic Nucleotides in the Artificially Stimulated Decidual Cell Reaction in the Mouse Uterus.- 13. Inhibitory Effect of Indomethacin on Nuclear Binding of Progesterone in the Uterus and on Differentiation of Decidual Cells in Culture.- 14 Maternal Recognition of Pregnancy in Swine.- 15 Effects of Preimplantation Bovine and Porcine Conceptuses on Blood Flow and Steroid Content of the Uterus.- 16. Effects of Nicotine on Conceptus Cell Proliferation and Oviductal/Uterine Blood Flow in the Rat.- 17. The Uterine Epithelium as a Transducer for the Triggering of Decidualization in the Rat.- 18. Cellular Contact between the Trophoblast and the Endometrium at Implantation in the Ewe.- 19. Cell Motility and the Distribution ofActin and Myosin during Mouse Trophoblast Development in Vitro.- 20. Autoradiographic Studies of Mouse Uterine Glands during the Periimplantation Period.- 21 In Vitro Attachment and Outgrowth of Mouse Trophectoderm.- 22. Hormone Production by Rat Blastocysts and Midpregnancy Trophoblasts in Vitro.- 23. Separation and Characterization of Endocervical Cells.- 24. Role of the Major Histocompatibility Complex in the Timing of Early Mammalian Development.- 25. Pregnancy-Associated Endometrial Protein in Women.- 26. Survival of Rat Blastocysts in the Uterus of the Mouse Following Xenogeneic Implantation.- 27. Concanavalin-A-Binding Capacity of Preimplantation Mouse Embryos.- 28. The Use of Pharmacological Agents to Study Implantation.- Participants.