A possible role of aryl hydrocarbon receptor in spontaneous preterm birth

Yan Li, Kai Wang, Qing Yun Zou, Chi Zhou, Ronald R. Magness, Jing Zheng

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)494-497
Number of pages4
JournalMedical Hypotheses
Volume84
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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