title: Iron-dependent oxidative stress as a pathogenesis for preterm birth.
abstract: OBJECTIVE
  Preterm birth (PTB) is an oxidative stress-related disease that lacks effective therapies partly because of the poor understanding of disease pathogenesis. The aim of this manuscript was to review molecular pathways that could be responsible for the pathogenesis of PTB. Genomic and proteomic studies have started to delineate the wide array of mediators involved in this disorder. Understanding the mechanisms of the development of PTB and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for this disorder.
  
  
  METHODS
  This article reviews the English language literature for pathogenesis and pathophysiological studies on PTB. Several recent genomic and proteomic studies are discussed in the context of PTB biology.
  
  
  RESULTS
  Decidual hemorrhage has been identified histologically in the placentas of patients with PTB, which may result in high levels of free heme and iron. Several important PTB-specific genes and proteins overlap with those known to be regulated by iron. Others were genes involved in oxidative stress and detoxification. Free iron oxidatively modifies lipid and protein, leading to DNA and cell damage. This signaling pathway of PTB will be discussed as it provides new insights into regulation of inflammation, oxidative stress, and detoxification.
  
  
  CONCLUSIONS
  This review summarizes recent advances in heme/iron-mediated signaling, the target genes thereof, and the potential challenges to the understanding of pathogenesis and pathophysiology of PTB. A novel model is proposed. Collectively, decidual hemorrhage and inflammation are considered to be major contributors to the pathogenesis of PTB.
  
  
  BACKGROUND
  Obstetricians & Gynecologists, Family Physicians.
  
  
  OBJECTIVE
  After completion of this article, the reader should be able to paraphrase the role of oxidative stress in pathogenesis of preterm birth, explain the idea of preterm birth as a "syndrome," and summarize the potential role of early uterine bleeding in pathophysiology of preterm birth.
authors.affiliation: Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sado
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitanaka
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Shozo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shigetomi
authors.forename: Akira
authors.initials: A
authors.lastname: Onogi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Oi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D010447:Peptide Hydrolases / Q000097:blood; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction; D014592:Uterine Hemorrhage / Q000150:complications*
chemical_list: D016207:Cytokines; D007501:Iron; D010447:Peptide Hydrolases