title: Cumulus cell-expressed type I interferons induce cumulus expansion in mice.
abstract: Ovulation resembles the inflammatory response. The purpose of the present study was to examine the expression and role of type I interferons (IFNs) Ifnalpha and Ifnbeta in mouse ovaries during the process of ovulation. An in vivo injection of equine chorionic gonadotropin (CG)-human CG (hCG) stimulated Ifnalpha and Ifnbeta mRNA in cumulus-oocyte complexes (COCs) within 6 h. Type I IFN receptor (Ifnar1 and Ifnar2) genes were also expressed in preovulatory follicles without a change by hCG. Immunofluorescent study revealed the expression of protein signals of Ifnalpha, Ifnbeta, and Ifnar1 in cumulus cells. Treatment of COCs with Ifnalpha or Ifnbeta in vitro induced cumulus expansion that was comparable to that mediated by epiregulin. In cultured COCs, the levels of Ifnalpha and Ifnbeta mRNA increased by epiregulin and follicle-stimulating hormone, but not by prostaglandin E2. Ifnalpha and Ifnbeta activated multiple signaling events (signal transducer and activator of transcription-1/3, Akt, and mitogen-activated protein kinase 1/2) and stimulated the expression of genes known to impact COC expansion (Has2, Ptx3, Tnfaip6, and Ptgs2). Interestingly, treatment of COCs with Toll-like receptor (TLR) 2 and TLR4 ligands (lipopolysaccharides, Pam3Cys, and hyaluronan fragments) increased Ifnalpha and Ifnbeta mRNA, while coculture with anti-TLR2/4 neutralizing antibody abolished these effects. Taken together, these results demonstrate that the type I IFN system is operating in mouse cumulus cells and plays a role in the induction of cumulus expansion during the ovulatory process in mice.
authors.affiliation: School of Biological Sciences & Technology, Faculty of Life Science, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: You-Jee
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Animal Facility of Aging Science, Korea Basic Science Institute, Gwangju, Republic of Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Park
authors.affiliation: Animal Facility of Aging Science, Korea Basic Science Institute, Gwangju, Republic of Korea.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Moon
authors.affiliation: School of Biological Sciences & Technology, Faculty of Life Science, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Phuong T M
authors.initials: PT
authors.lastname: Dam
authors.affiliation: Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Cho
authors.affiliation: School of Biological Sciences & Technology, Faculty of Life Science, Chonnam National University, Gwangju, Republic of Korea sychun@jnu.ac.kr.
authors.forename: Sang-Young
authors.initials: SY
authors.lastname: Chun
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007370:Interferon Type I / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010060:Ovulation / Q000502:physiology
chemical_list: D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D007370:Interferon Type I
keywords: TLR-2/4; cumulus expansion; gonadotropins; ovulation; type I interferons