title: Tumor necrosis factor alpha partially contributes to lipopolysaccharide-induced intra-uterine fetal growth restriction and skeletal development retardation in mice.
abstract: Maternal infection is a cause of adverse developmental outcomes. Lipopolysaccharide (LPS)-induced embryonic resorption, intra-uterine fetal death (IUFD) and preterm labor have been well characterized. In the present study, we investigated the effects of maternal LPS exposure on intra-uterine fetal growth and skeletal development. All pregnant mice except controls received an intraperitoneal injection of LPS (75 microg/kg) on gestational days (GD) 15-17. The number of live fetuses, dead fetuses and resorption sites was counted on GD 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. As expected, perinatal LPS exposure resulted in 63.2% fetal death. LPS significantly lowered fetal weight, reduced crown-rump and tail lengths, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone. Additional experiment showed that a single dose of LPS (75 microg/kg, i.p.) on GD 15 increased the expression of TNF-alpha mRNA in maternal liver and placenta and TNF-alpha concentration in maternal serum and amniotic fluid. Furthermore, pentoxifylline, an inhibitor of TNF-alpha synthesis, significantly inhibited TNF-alpha production, reduced fetal mortality, and reversed LPS-induced fetal intra-uterine growth restriction and skeletal development retardation. Taken together, these results suggest that TNF-alpha is, at least in part, involved in LPS-induced intra-uterine fetal death, intra-uterine growth restriction and skeletal development retardation.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, PR China. xudex@mail.hf.ah.cn
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation; D020567:Fetal Weight / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008813:Mice, Inbred ICR; D010012:Osteogenesis / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione