title: Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage.
abstract: During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus.
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: dongyupeng7@gmail.com.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Obstetrics & Gynecology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Velayo
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Sugibayashi
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kiyoe
authors.initials: K
authors.lastname: Funamoto
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kudo
authors.initials: K
authors.lastname: Hitomi
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Iida
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Endo
authors.affiliation: Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Obstetrics & Gynecology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D051698:Activating Transcription Factor 2 / Q000032:analysis / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005333:Fetus / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020300:Intracranial Hemorrhages / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D015427:Reperfusion Injury / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology; D014621:Vagina / Q000276:immunology*
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53
keywords: ATF2; FECG; Fetal brain hemorrhage; Ischemic reperfusion; LPS; P53