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Mechanisms By Which Mumps Virus Infection Perturbs Mouse Ovarian Function

Posted on:2017-05-07Degree:MasterType:Thesis
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:2284330488967709Subject:Cell biology
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Background and objectives:Mumps virus (MuV) infection may lead to oophoritis and perturb ovarian function; the underlying mechanisms remain unclear. This thesis focuses on the pattern recognition receptor (PRR)-initiated innate immune responses to MuV infection in ovarian granulosa cells and their effects on ovarian functions in mice.Materials and Methods:Toll-like receptor 2 knockout (TLR2-/-) mice and RNA interfering approaches were used to investigate gene function. Gene expression at mRNA level was examined using real-time qRT-PCR. Immunohistochemistry and Western blot were used for the determination of protein distribution and quantification. The cytokine, estradiol and testosterone levels were measured using ELISA. Intraperitoneal injection of MuV was used to examine the ovarian innate immune responses in vivo.Results:Ovarian granulosa cells infected with MuV significantly produced pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor a (TNF-a), and monocyte chemotactic protein 1 (MCP-1), as well as type 1 interferons (IFN-a and IFN-β). Knockdown of RIG-I significantly decreased MuV-induced cytokine expression. TLR2 deficiency reduced the expression of IL-1β, TNF-a, and MCP-1 but did not affect the expression of IFN-a and IFN-β in granulosa cells after infection with MuV. Intraperitoneal injection of MuV induced the ovarian innate immune responses in vivo, which suppressed estradiol synthesis and induced granulosa cell apoptosis.Conclusions:MuV infection induces the innate immune responses in mouse ovarian granulosa cells through TLR2 and RIG-I signaling. The MuV-indued ovarian innate immune responses significantly reduced the estradiol levels and induced granulosa cell apoptosis. These results provide novel insights into the mechanisms underlying MuV-impaired ovarian function in mice.
Keywords/Search Tags:Mumps virus, granulosa cell, innate immune response, pattern recognition receptor, ovarian function
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