Ovulation as danger signaling event of innate immunity. Spanel-Borowski K et al. 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.
Expression regulated by
LH
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Ovarian localization
Cumulus
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Induced expression of pattern recognition receptors (PRRs) in cumulus oocyte complexes (COCs): Novel evidence for innate immune-like functions during ovulation. Shimada M et al. Ovulation is the complex, inflammatory-like process by which the cumulus oocyte complex (COC) is released from a mature, preovulatory (PO) follicle through a rupture site at the ovarian surface and requires expression of genes that generate and stabilize the expanded extracellular COC matrix. Gene profiling analyses of COCs at selected time intervals during ovulation revealed that many genes associated with immune related surveillance functions were also induced in cumulus cells. Specifically, cell surface signaling molecules known as pattern recognition receptors (PRRs) that act as sensors of the external environment important for the innate immune system to detect 'self' from 'non-self' or 'altered self' are induced and/or expressed in cumulus cells as well as granulosa cells. These include the complement factor C1q, CD14 and the Toll-like receptors (TLRs) 4, 8 and 9 as well as mediators of TLR activation, MYD88 and IRF3. COCs exposed to bacterial LPS exhibit enhanced phosphorylation of p38MAPK, ERK1/2 and NF-kB and increased expression of Il6 and Tnfa target genes, documenting that the TLR pathway is functional. Cumulus cells and granulosa cells also express the scavenger receptors CD36 and SCARBI and exhibited phagocytic uptake of fluorescently-tagged bacterial particles. Collectively, these results provide novel evidence that cumulus cells as well as granulosa cells express innate immune related genes that may play critical roles in surveillance and cell survival during the ovulation process.