title: Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.
abstract: In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero.
authors.affiliation: Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kusama
authors.affiliation: Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, Japan.
authors.forename: Rulan
authors.initials: R
authors.lastname: Bai
authors.affiliation: Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Yasuda
authors.affiliation: Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C020947:interferon tau; D046988:Proteasome Endopeptidase Complex