Induced expression of pattern recognition receptors in cumulus oocyte complexes: novel evidence for innate immune-like functions during ovulation.
Ovulation is the complex, inflammatory-like process by which the cumulus oocyte complex (COC) is released from a mature, preovulatory 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 that act as sensors of the external environment important for the innate immune system to detect self from nonself or altered self are induced and/or expressed in cumulus cells as well as granulosa cells. These include the complement factor q1, CD14, and the Toll-like receptors (TLRs) 4, 8, and 9 as well as mediators of TLR activation, myeloid differentiation primary response gene 88 and interferon regulatory factor 3. COCs exposed to bacterial lipopolysaccharide exhibit enhanced phosphorylation of p38MAPK, ERK1/2 and nuclear factor-kappaB 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 scavenger receptor type B1 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.
Shimada
Masayuki
M
Department of Molecular Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Hernandez-Gonzalez
Inmaculada
I
Gonzalez-Robanya
Ignacio
I
Richards
Joanne S
JS
D066258:Amphiregulin; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D015922:Complement C1q / Q000235:genetics; D066255:EGF Family of Proteins; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000276:immunology*; D010060:Ovulation / Q000235:genetics* / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*
D066258:Amphiregulin; C587849:Areg protein, mouse; D018955:CD36 Antigens; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D015922:Complement C1q; D005640:Follicle Stimulating Hormone; D020928:Mitogen-Activated Protein Kinases