A possible role of aryl hydrocarbon receptor in spontaneous preterm birth

Abstract Preterm birth (PTB) is defined as birth before 37 weeks of gestation and is a leading cause of neonatal mortality and morbidity. To date, the etiology of spontaneous PTB (sPTB) remains unclear; however, intrauterine bacterial infection-induced inflammation is considered to be one of the maj...

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Bibliographic Details
Published in:Medical hypotheses 2015-05, Vol.84 (5), p.494-497
Main Authors: Li, Yan, Wang, Kai, Zou, Qing-Yun, Zhou, Chi, Magness, Ronald R, Zheng, Jing
Format: Article
Language:English
Subjects:
Cyclooxygenase 2 - metabolism
Female
Humans
Internal Medicine
Models, Biological
Placenta - metabolism
Pregnancy
Premature Birth - etiology
Prostaglandins - metabolism
Receptors, Aryl Hydrocarbon - metabolism
Signal Transduction - physiology
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Summary:Abstract Preterm birth (PTB) is defined as birth before 37 weeks of gestation and is a leading cause of neonatal mortality and morbidity. To date, the etiology of spontaneous PTB (sPTB) remains unclear; however, intrauterine bacterial infection-induced inflammation is considered to be one of the major triggers. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor. Upon activation, AhR signaling mediates many biological processes. AhR is abundantly expressed in human placentas, primarily in trophoblasts, and several fetal organs and tissues. The activation of AhR signaling can modulate inflammatory responses via promoting production of pro-inflammatory cytokines by the placenta and fetal membranes. These cytokines could enhance expression and/or activity of cyclooxygenase-2 (COX2) in human trophoblasts and amniotic epithelia, which in turn stimulate synthesis and release of prostaglandins (PGs; e.g., PGE2 and PGF2α). Given the discovery of a number of natural and endogenous AhR ligands in human, we hypothesize that in a subset of patients with high AhR expression in placentas and fetal membranes, repeated exposure to these AhR ligands hyperactivates AhR, inducing hyperactivation of the cytokines/COX2/PGs pathway, resulting in myometrial contractions, ultimately leading to sPTB. We further hypothesize that hyperactivation of this AhR pathway can induce sPTB either directly or in synergy with the bacterial infection. Proof of this hypothesis may provide a novel mechanism underlying sPTB.
ISSN:0306-9877
1532-2777
DOI:10.1016/j.mehy.2015.02.001