title: Polyinosinic-polycytidylic acid initiates ovarian innate antiviral response and inhibits steroidogenesis in female mice.
abstract: Viral infection may perturb ovarian functions. However, innate antiviral response in the ovary has not been intensively investigated. In this study, we examined the innate antiviral system in the mouse ovary and the impacts of antiviral response on steroidogenesis. Major virus sensors, including Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I, and melanoma differentiation-associated gene 5, are predominantly expressed in ovarian stromal and granulosa cells. Polyinosinic-polycytidylic acid (poly [I:C]) is a common agonist of TLR3, retinoic acid-inducible gene I, and melanoma differentiation-associated gene 5. Intraperitoneal injection of poly (I:C) activated nuclear factor kappa B and interferon (IFN) regulatory factor 3 in the ovarian cells and induced the expression of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and type 1 IFNs (IFNA/B). Moreover, poly (I:C) upregulated the expression of several antiviral proteins, including 2'-5'-oligoadenylate synthetase, IFN-stimulated gene 15, and Mx GTPase 1. The innate antiviral response in the ovary was significantly reduced in Tlr3-deficient mice. Notably, we demonstrated that poly (I:C) injection inhibits steroidogenesis enzyme expression and decreases plasma estradiol and testosterone levels. The results show that the mouse ovary is equipped with innate antiviral state, and the antiviral response perturbs ovarian endocrine function.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Liu
authors.forename: Shutao
authors.initials: S
authors.lastname: Zhao
authors.forename: Lijing
authors.initials: L
authors.lastname: Cheng
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D007113:Immunity, Innate / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010053:Ovary / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014780:Viruses / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D012739:Gonadal Steroid Hormones; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D011070:Poly I-C
keywords: innate antiviral response; ovary; pattern recognition receptor; steroidogenesis