Full Description
The monograph introduces innate immunity as second authority in the ovary besides the endocrine system. Innate immunity appears to orchestrate follicular atresia, follicle rupture, follicle transformation into a corpus luteum (CL) and CL regression through nonsterile inflammation and tissue repair. The concept is new. It centres on cytokeratin-positive (CK+) cells being recognized as a potential nonlymphoid dendritic cell type (DC). Part I describes morphological aspects of immune privilege starting with active hamster ovary implants into the chicken chorioallantois membrane. Follicular atresia and follicle rupture correspond with mild and moderate tissue damage in ovaries of small rodents and rabbits. Superovulations cause severe tissue damage through intraovarian oocyte release with follicle wall remnants in oedema, rupture of vessel walls and thrombosis. The complement system and neuropeptides might play regulatory roles. Part IIa analyzes intact ovaries (cows, human) for the appearance of CK+ cells. In the foetal ovary, sex cords give rise to CK+ cells in primordial follicles. In the adult ovary, CK+ cells are absent in preantral follicles and reappear in mature and regressing follicles. In the CL of early development, steroidogenic CK+ cells build a peripheral zone in the previous granulosa cell layer, and uniformly distribute in the following stages. A microvessel-associated CK+ cell type is seldom found. Part IIb characterizes the morphology and function of CK+ cells in vitro. Isolated from human preovulatory follicles, the epithelioid CK+ granulosa cell subtype regulates TLR4 and CD14 at 36 h of treatment with oxidized lipoprotein (oxLDL, 150 mg/ml); nonapoptotic cell death and the increase of reactive oxygen species occur. In contrast, the CK-negative (CK-) granulosa cell type regulates the lectin-like oxLDL receptor 1 (LOX-1) and survival autophagy under oxLDL stimulation. Isolated from bovine CL, the epithelioid CK+ cell type 1 is disclosed asmicrovascular cell type with a single nonmotile cilium. The microvascular CK+ type strongly upregulates intercellular contacts under treatment with interferon- (IFN-). In the CK- cell type 5 of granulosa cell -like appearance, IFN- treatment supports cell proliferation, N-cadherin upregulation, and the dramatic increase in major histocompatibility complex II peptides (MHC II) by 80-fold compared to basal levels. Type 5 could have been conversed from the steroidogenic CK+ cell type. We summarize and conclude: CK+ granulosa cells express functionally active TLR4, which sense danger signals like oxidative stress in preovulatory follicles and trigger inflammatory and immunoregulatory pathways. The final outcome regulates follicle rupture and transformation into CL. Luteolysis could start by danger-sensing through the microvascular CK+ type 1 cells and the DC-like type 5 cells both sensitive to IFN-. The future will witness a novel strategy in the therapy of ovarian disorders like anovulations, luteal phase insufficiency, and autoimmune failures
Contents
1 Background.- 1.1 Innate Immunity, Toll-like Receptors (TLR), and Danger Signals 1.2 The Ovary, Tissue Remodelling, and Immune Privilege.- 1.3 Design.- 2 Material and Methods.- 2.1 Cyclic and Superovulated Ovaries from Rats, Hamsters, Rabbits as well as Canine, Bovine and Human Ovaries.- 2.1.1 Fibrinolytic Activity and Implants on the Chick Chorioallantois Membrane (CAM).- 2.1.2 Fixation, Staining and Counting Ovarian Structures.- 2.2 Cell Culture Subtypes from Follicles Derived from Patients Under in Vitro Fertilization Therapy.- 2.3 Cell Culture Subtypes from Bovine Corpus Luteum (CL) and Characterization.- 3 Footmarks of Innate Immunity.- 3.1 The Complement System as Danger Sensor in General and in the Ovary.- 3.2 Mild Danger with Mild Response.- 3.2.1 Implantation of the Ovary into the CAM.- 3.2.2 Follicular Atresia.- 3.3 Moderate Danger by Preovulatory Follicle Rupture and Acute Inflammation with Eosinophils.- 3.3.1 Recruitment of Eosinophils and Substance P-Like Expression.- 3.4 Severe Danger in Superovulated Ovaries with Intra-Ovarian Oocyte Release and Thrombus Formation.- 4 Cytokeratin-Positive (CK+) cell as Potential Dendritic Cells.- 4.1 Dendritic cells, the TLR System in General and in the Ovary.- 4.2 Localisation of CK+ Cells in the Intact Ovary.- 4.2.1 Follicles in Foetal and Adult Ovaries.- 4.2.2 Corpus Luteum.- 5 Characterization of Isolated CK+ Cells.- 5.1 CK+ Cells from Preovulatory Follicles with TLR4 Expression.- 5.2 CK+ Cells from CL in Comparison to CK-Negative (CK-) Cells.- 5.2.1 Effects of Interferon-gamma on CK+ Cells from the CL Compared to CK- Cells and to Surface Epithelial Cells.- 5.2.2 Reflections on Quality of the CK+ Type 1 and Similarity with the Type 5.- 6 Working Hypothesis and Challenges.- 7 Clinical Perspectives.- 8 Concluding Summary and Remarks.- References.- Subject index.
