title: Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.
abstract: Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.
authors: Bioactive Lipids Research Program, Department of Pathology, Lipidomics Core Facility, and maddipati@wayne.edu.
authors: Krishna Rao
authors: KR
authors: Maddipati
authors: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA; Department of Epidemiology, Michigan State University, East Lansing, Michigan, USA;
authors: Roberto
authors: R
authors: Romero
authors: Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA; Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA;
authors: Tinnakorn
authors: T
authors: Chaiworapongsa
authors: Bioactive Lipids Research Program, Department of Pathology, Lipidomics Core Facility, and.
authors: Sen-Lin
authors: SL
authors: Zhou
authors: Department of Computer Science, Wayne State University, Detroit, Michigan, USA;
authors: Zhonghui
authors: Z
authors: Xu
authors: Department of Computer Science, Wayne State University, Detroit, Michigan, USA;
authors: Adi L
authors: AL
authors: Tarca
authors: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Sótero del Río Hospital, Santiago, Chile; and.
authors: Juan Pedro
authors: JP
authors: Kusanovic
authors: University of Chile, Santiago, Santiago, Chile.
authors: Hernan
authors: H
authors: Munoz
authors: Bioactive Lipids Research Program, Department of Pathology.
authors: Kenneth V
authors: KV
authors: Honn
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D010088:Oxidoreductases / Q000378:metabolism*; D011247:Pregnancy; D047929:Term Birth / Q000378:metabolism* / Q000502:physiology
chemical_list: D015777:Eicosanoids; D016718:Arachidonic Acid; D010088:Oxidoreductases
keywords: LC-MS; epoxy fatty acids; hydroxy fatty acids; lipidomics; parturition