Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative stress in a mouse model of preterm labor.
OBJECTIVE
Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of ω-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 μM) and analyzed for oxidative stress.


RESULTS
In vivo. Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (P<0.05-0.01) and increased tumor necrosis factor-α in the uterus (P<0.05) and amniotic fluid (P<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<0.035). However, no differences in oxidative stress were observed in the amniotic fluid. In vitro. Treatment of macrophage-like cells with ω-3 PUFA significantly and dose-dependently increased oxidative stress (P<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.
Tharwat Stewart
TS
Boulis
Burton
B
Rochelson
Olivia
O
Novick
Xiangying
X
Xue
Prodyot K
PK
Chatterjee
Madhu
M
Gupta
Malvika H
MH
Solanki
Meredith
M
Akerman
Christine N
CN
Metz
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D019587:Dietary Supplements / Q000009:adverse effects*; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects*; D005260:Female; D051379:Mice; D007752:Obstetric Labor, Premature / Q000378:metabolism* / Q000517:prevention & control; D018384:Oxidative Stress; D011247:Pregnancy; D011897:Random Allocation
D015415:Biomarkers; D016207:Cytokines; D015525:Fatty Acids, Omega-3