Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation

Peroxisome proliferator-activated receptor (PPAR)-gamma is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-gamma agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 mu g/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-alpha, interleukin (11)-1 beta, 11-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNE-alpha and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-gamma signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-kappa B) activation and blocked nuclear translocation of NF-kappa B p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-gamma-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-gamma as an important regulator of placental inflammation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.