Toll-like 4 receptor /NFκB inflammatory/miR-146a pathway contributes to the ART-correlated preterm birth outcome

Abstract

Assisted reproductive technology (ART) is widely used for the women with infertility conditions to achieve pregnancy. However, the adverse effects of ART may lead to poor perinatal and neonatal outcomes, e.g., preterm birth and low body weight. In this study, we investigated the inflammatory molecular factors and microRNA that might be involved in ART related preterm birth. We found the elevation of Toll-like 4 receptor (TLR4), activation of NFκB pathway and down-regulation of microRNA-146a (miR-146a), a negative regulator of NFκB, in the placenta of preterm birth and ART, indicating preterm birth and ART were associated with inflammation signaling activation. In vitro experiments demonstrated that miR-146a suppressed NFκB pathway and shifted the balance of cytokines in the cord blood toward a repertoire of pro-inflammatory outcomes by down-regulating IRAK1 and TRAF6. The pro-inflammatory cytokines IL-6, IFNγ and TNFα in the cord blood were highly expressed in the preterm and ART, while anti-inflammatory cytokine IL-10 was the lower in the preterm and ART. In summary, we firstly uncovered that TLR4/NFκB mediated inflammation signaling and miR-146a participated in ART-related preterm birth patients, which suggests that importance of TLR4/NFκB/miR-146a signaling in clinical interventions and biomarkers of ART-related perinatal or neonatal outcomes.