title: Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.
abstract: Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 μg/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)-α, interleukin (Il)-1β, Il-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 TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, China.
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Bo
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, China; Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
authors.forename: Gui-Bin
authors.initials: GB
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China; Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, China. Electronic address: xudex@126.com.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018925:Chemokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: Fetal death; Inflammation; Lipopolysaccharide; Peroxisome proliferator-activated receptor-γ; Rosiglitazone