title: Ovulation as danger signaling event of innate immunity.
abstract: The ovulatory process is characterized by tissue wounding and, after oocyte expulsion, by healing being connected to the formation of a corpus luteum (CL). The ovulatory event thus compares with a sterile inflammation. The concept is forwarded that the ovulatory process depends on innate immunity (INIM) function. The ultimate trigger for INIM signaling are danger signals/alarmins from granulosa cells damaged by oxidative stress and reactive oxygen species (ROS), respectively. Alarmins like oxidized low density lipoprotein (oxLDL) are recognized by cytokeratin-positive (CK(+)) granulosa cells with the expression of toll-like receptor 4 (TLR4). The subsequent inside-out signaling from the antrum towards the thecal cell layer comprises inflammation and tissue disintegration, which might be dominated by the myeloid differentiation factor 88 (Myd88) gateway. Additive or co-regulatory function are expected from the complement cascade for vessel permeability and leukocyte immigration and the wingless (WnT)-signaling for cell adhesion of CK(+) granulosa cells. The outside-in signaling relates to the repair phase, which is primarily controlled by the TIR-domain-containing adaptor protein producing IFN type I (TRIF) gateway of TLR signaling. The KIT/CD117 tyrosine kinase receptor and the tachykinin-tachykinin receptor system could be involved. The appealing concept of INIM function in the ovary is novel and inaugurates a novel research field.
authors.affiliation: Institute of Anatomy, University of Leipzig, Leipzig, Germany. spanelb@medizin.uni-leipzig.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Spanel-Borowski
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D003338:Corpus Luteum / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D010060:Ovulation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008077:Lipoproteins, LDL; D053594:Myeloid Differentiation Factor 88; D017382:Reactive Oxygen Species; C470409:TICAM1 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051153:Wnt Proteins; D003165:Complement System Proteins