Iron-dependent oxidative stress as a pathogenesis for preterm birth.
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.
Sakata
Mariko
M
Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
Sado
Toshiyuki
T
Kitanaka
Takashi
T
Naruse
Katsuhiko
K
Noguchi
Taketoshi
T
Yoshida
Shozo
S
Shigetomi
Hiroshi
H
Onogi
Akira
A
Oi
Hidekazu
H
Kobayashi
Hiroshi
H
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*
D016207:Cytokines; D007501:Iron; D010447:Peptide Hydrolases