Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta

Toll-like receptor 2 and 4 mRNA expressions in COT tissue of control (C) and obese (OB) ewes on 75 dG ■: C ewes; □: OB ewes. Mean ± SEM; *: P < 0.05; †: P = 0.06; n = 10 in each group.

Macrophage markers CD11b, CD14 and CD68 and proinflammatory cytokines TNF-α, IL-6, IL-8 and IL-18 mRNA expressions in COT tissue of control (C) and obese (OB) ewes on 75 dG ■: C ewes; □: OB ewes. Mean ± SEM; **: P < 0.01; *: P < 0.05; †: P = 0.06; n = 10 in each group.

JNK and NF-κB inflammatory signaling pathway protein content and phosphorylation in COT tissue of control (C) and obese (OB) ewes on 75 dG ■: C ewes; □: OB ewes. Mean ± SEM; **: P < 0.01; *: P < 0.05, n = 10 in each group.

A hypothetical model for pathways linking maternal obesity to inflammation in placenta. Maternal obesity increases free fatty acids in fetal circulation, which activates TLR4 signaling and inflammatory signaling pathways, NF-κB and JNK pathways. As a result, the expression of inflammatory cytokines was increased, which further induces inflammation forming a vicious circle. TLR4: Toll-like receptor 4; NF-κB: Nuclear factor kappa B; JNK: Jun N-terminal kinase; AP-1: Activator protein 1.