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Omega-3 fatty acids suppress Fusobacterium nucleatum–induced placental inflammation originating from maternal endothelial cells
Jeewon Garcia-So, … , Kang Liu, Yiping W. Han
Jeewon Garcia-So, … , Kang Liu, Yiping W. Han
Published February 7, 2019
Citation Information: JCI Insight. 2019;4(3):e125436. https://doi.org/10.1172/jci.insight.125436.
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Research Article Microbiology

Omega-3 fatty acids suppress Fusobacterium nucleatum–induced placental inflammation originating from maternal endothelial cells

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Abstract

Fusobacterium nucleatum is an oral anaerobe prevalent in intrauterine infection associated with a wide spectrum of adverse pregnancy outcomes. We demonstrate here that F. nucleatum triggers placental inflammation through maternal, rather than paternal, TLR4-mediated signaling. Elimination of TLR4 from maternal endothelial cells alleviated placental inflammation and reduced fetal and neonatal death, while elimination of TLR4 in the hematopoietic cells had no effect. The placental inflammatory response followed a spatiotemporal pattern, with NF-κB activation observed first in the maternal endothelial cells and then in the decidual cells surrounding the endothelium, followed by induction of inflammatory cytokines and chemokines. Supplementation of pregnant mice with fish oil as a source of omega-3 fatty acids suppressed placental inflammation, reduced F. nucleatum proliferation in the placenta, and increased fetal and neonatal survival. In vitro analysis illustrates that omega-3 fatty acids inhibit bacterial-induced inflammatory responses from human umbilical cord endothelial cells. Our study therefore reveals a mechanism by which microbial infections affect pregnancy and identifies a prophylactic therapy to protect against intrauterine infections.

Authors

Jeewon Garcia-So, Xinwen Zhang, Xiaohua Yang, Mara Roxana Rubinstein, De Yu Mao, Jan Kitajewski, Kang Liu, Yiping W. Han

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Figure 2

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F.
nucleatum–induced placental inflammation originates from the materna...
nucleatum–induced placental inflammation originates from the maternal endothelial cells. Approximately 107 CFU F. nucleatum 12230 or saline was injected into the tail vein of each C57BL/6 pregnant dam on day 16 or 17 of gestation. (A) The fetal and neonatal death rate was calculated as the percentage of dead fetuses and neonates per litter at birth and followed up to 3 days after birth. Genotypes of the mating parents are shown below the x axis. Each geometric symbol represents 1 pregnant mouse. The horizontal lines indicate the average death rates. (B) mRNA levels in the placentas measured by real-time quantitative PCR and expressed as fold changes compared with each genotypes’ own saline-injected control groups. At least 3 pregnant dams were included in each group. (C) Protein levels of IL-1β in the placentas, as determined by ELISA. At least 3 pregnant dams were included in each group. For B and C, the placentas were collected at 48 hours after injection and pooled for each pregnant dam. The results are presented as dot plots with average and SEM. Two-way ANOVA was performed with simple-effects analysis when the interaction was significant. Student-Newman-Keuls was applied for post-hoc comparisons. *P < 0.05, **P < 0.01, ***P < 0.001. D, Dam; S, Sire.

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