title: Effects of maternal n-3 fatty acid supplementation on placental cytokines, pro-resolving lipid mediators and their precursors.
abstract: The aim of this study was to determine whether supplementation with fish oil-derived n-3 polyunsaturated fatty acids (n-3 PUFA) during pregnancy modifies placental PUFA composition, the accumulation of specialised pro-resolving lipid mediators (SPMs, specifically resolvins (Rv), protectins (PD) and upstream precursors) and inflammatory gene expression. Placentas were collected from women (n=51) enrolled in a randomised, placebo controlled trial of n-3 PUFA supplementation from 20-week gestation. Lipids were extracted for fatty acid analysis and SPMs were quantitated by mass spectrometry. Gene expression was determined by qRT-PCR. Using multiple regression analysis, data were correlated for placental n-3 PUFA and SPM levels with PUFA levels in maternal and cord blood erythrocytes. Supplementation with n-3 PUFAs increased placental docosahexaenoic acid (DHA) levels, but not eicosapentaenoic acid (EPA) levels (P<0.05), and increased the levels of the SPM precursors 18-hydroxyeicosapentaenoic acid and 17-hydroxydocosahexaenoic acid (17-HDHA) by two- to threefold (P<0.0005). RvD1, 17R-RvD1, RvD2 and PD1 were detectable in all placentas, but concentrations were not significantly increased by n-3 PUFA supplementation. Placental DHA levels were positively associated with maternal and cord DHA levels (P<0.005), and with placental 17-HDHA concentrations (P<0.0001). Placental mRNA expression of PTGS2, IL1β, IL6 and IL10 was unaffected by n-3 PUFA supplementation, but TNFα expression was increased by 14-fold (P<0.05). We conclude that n-3 PUFA supplementation in pregnancy i) enhances placental accumulation of DHA and SPM precursors, ii) does not alter placental EPA levels, and iii) has no stimulatory effects on inflammatory gene expression. Further studies are required to ascertain the biological significance of SPMs in the placenta and the potential immunomodulatory effects of elevating placental SPM levels.
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia Jeff.keelan@uwa.edu.au.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Keelan
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Nina
authors.initials: N
authors.lastname: D'Vaz
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Dunstan
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Shaofu
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mark
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Waddell
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Prescott
authors.affiliation: School of Women's and Infants' HealthKing Edward Memorial Hospital, University of Western Australia, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of Medicine and PharmacologyRoyal Perth Hospital, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, AustraliaSchool of Paediatrics and Child HealthTelethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Perth, Western Australia 6008, AustraliaSchool of AnatomyPhysiology and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D016207:Cytokines / Q000032:analysis*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000032:analysis; D015118:Eicosapentaenoic Acid / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D007249:Inflammation / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects*; D010919:Placebos; D010920:Placenta / Q000737:chemistry* / Q000187:drug effects; D011247:Pregnancy
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D010919:Placebos; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid