title: Obox4-silencing-activated STAT3 and MPF/MAPK signaling accelerate nuclear membrane breakdown in mouse oocytes.
abstract: Mouse oocytes begin to mature in vitro once liberated from ovarian follicles. Previously, we showed that oocyte-specific homeobox 4 (Obox4) is critical for maintaining the intact nuclear membrane of the germinal vesicle (GV) in oocytes and for completing meiosis at the metaphase I-II (MI-MII) transition. This study further examines the molecular mechanisms of OBOX4 in regulating GV nuclear membrane breakdown. Maturation-promoting factor (MPF) and MAPK are normally inactive in GV stage oocytes but were activated prematurely in arrested GV stage oocytes by 3-isobutyl-1-metyl-xanthine (IBMX) in vitro after Obox4 RNA interference (RNAi). Furthermore, signal transducer and activator of transcription 3 (STAT3) was significantly activated by Obox4 RNAi. We confirmed that this Obox4 RNAi-induced premature STAT3 and MPF/MAPK activation at the GV stage provoked subsequent GV breakdown (GVBD) despite the opposing force of high cAMP in the IBMX-supplemented medium to maintain intact GV. When cumulus-oocyte complexes were exposed to interferon α (IFNA), a STAT3 activator, oocytes matured and cumulus cells expanded to resume nuclear maturation in IBMX-supplemented medium, suggesting that STAT3 activation is sufficient for stimulating the continuation of meiosis. Using Stattic, a specific STAT3 inhibitor, we confirmed that GVBD involves STAT3 activation in Obox4-silenced oocytes. Based on these findings, we concluded that i) Obox4 is an important upstream regulator of MPF/MAPK and STAT3 signaling, and ii) Obox4 is a key regulator of the GV arrest mechanism in oocytes.
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea.
authors.forename: Hyun-Seo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea.
authors.forename: Kyeoung-Hwa
authors.initials: KH
authors.lastname: Kim
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea.
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea.
authors.forename: Jung-Jae
authors.initials: JJ
authors.lastname: Ko
authors.affiliation: DNA Repair Research CenterChosun University, Gwangju, KoreaDepartment of Biomedical ScienceCollege of Life Science, CHA University, CHA Bio Complex, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Korea leeka@cha.ac.kr.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008540:Meiosis / Q000502:physiology; D000090204:Mesothelin; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; C000715528:Msln protein, mouse; C499222:Obox4 protein, mouse; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D000090204:Mesothelin