title: 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 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.
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, United States.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Zou
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, United States; Department of Pediatrics, University of Wisconsin, Madison, WI 53715, United States; Department of Animal Sciences, University of Wisconsin, Madison, WI 53715, United States.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Magness
authors.affiliation: Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, United States; Department of Cardiovascular Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong, PR China. Electronic address: jzheng@wisc.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
mesh_terms: D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology*; D011453:Prostaglandins / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D018336:Receptors, Aryl Hydrocarbon; D051546:Cyclooxygenase 2