Fusobacterium Nucleatum-Induced Placental Inflammation Originates from Maternal Endothelial Cells Which Can Be Suppressed by Omega-3 Fatty Acids

JEEWON SO; MARA ROXANA RUBINSTEIN; KANG LIU; YANG XIAOHUA; JAN KITAJEWSKI; XINWEN ZHANG; DE YU MAO; YIPING W HAN

Paris

Conferencia; 66th Annual Scientific Meeting Society for Reproductive Investigation; 2019

Society for Reproductive Investigation

Introduction: Fusobacterium nucleatum is an oral anaerobe prevalentin intrauterine infection associated with a wide spectrum of pregnancycomplications. We demonstrate here the origin of placental inflammationand that omega-3 fatty acid supplementation inhibits F. nucleatum-inducedplacental infection and inflammation.Methods: Using whole-body and tissue-specific Toll-like receptor 4(TLR4) knockout mice, we investigated the role of TLR4 in mediatingplacental inflammation in different cell types. We also examined theeffect of omega-3 fatty acids supplementation on birth outcomes in mice.Results: F. nucleatum triggers placental inflammation through TLR4-mediated signaling in maternal endothelial cells that lead to fetal andneonatal demise. Supplementation of pregnant mice with fish oil as asource of omega-3 fatty acids during gestation suppresses placentalinflammation, reduces F. nucleatum proliferation in the placenta, andincreases fetal and neonatal survival. In vitro analysis illustrates thatomega-3 fatty acids inhibit bacterial-induced inflammatory responsesfrom human umbilical cord endothelial cells.Conclusion: Our study reveals a novel mechanism by which microbialinfections affect pregnancy and identifies a prophylactic therapy to protectagainst intrauterine infections.