Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative stress in a mouse model of preterm labor

Objective: Omega-3 polyunsaturated fatty acid (omega-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of omega-3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of preterm labor. Methods: In vivo. Female Swiss Webster mice were fed a normal diet or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On gestational day 15, dams were injected with either saline (n = 10 per group) or lipopolysaccharide (LPS, intrauterine) (n = 10 per group). Maternal plasma, amniotic fluid, placentas, and uteri were collected 4 h later and assessed for cytokines; maternal plasma and amniotic fluids were analyzed for oxidative stress. In vitro. RAW264.7 mouse macrophage-like cells were treated with either: vehicle, H2O2, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) -(0, -0.1-100 mu M) and analyzed for oxidative stress. Results: In vivo. Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (P \u3c 0.05-0.01) and increased tumor necrosis factor-a in the uterus (P \u3c 0.05) and amniotic fluid (P \u3c 0.01) when compared to LPS-treated normal-fed animals. Maternal plasma obtained from FO-fed dams showed higher LPS-induced oxidative stress than control-fed animals (P \u3c 0.035). However, no differences in oxidative stress were observed in the amniotic fluid. In vitro. Treatment of macrophage-like cells with omega-3 PUFA significantly and dose-dependently increased oxidative stress (P \u3c 0.001-0.0001). Conclusions: Supplementation with FO for prior to and during pregnancy significantly increased LPS-induced inflammation in the amniotic fluid, uterus, and placenta and significantly increased maternal systemic oxidative stress in vivo. Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in vitro