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Submitted on May 8, 2006
Accepted on August 18, 2006
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030 (MS, I H-G, I G-R, JSR), Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama Higashi-Hiroshima, 724-8528, Japan (MS), Departments of Biochemistry and Molecular Biology and Physiology, Faculty of Sciences, University of Las Palmas, 35016 Las Palmas Grand Canaria, Spain (I H-G, I G-R)
* To whom correspondence should be addressed. E-mail: joanner{at}bcm.tmc.edu.
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.
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