title: Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy induces TLR4 activation in the placenta contributing to preeclampsia.
abstract: Balanced immune responses are essential for the maintenance of successful pregnancy. Aberrant responses of immune system during pregnancy increase the risk of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface. This study aimed to generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist) administration on gestational day (GD) 5 as rats are subjected to placentation immediately after implantation between GDs 4 and 5, and to assess the contribution of TLR4 signaling to the development of preeclampsia. Single administration of 0.5 μg/kg LPS significantly increased blood pressure of pregnant rats since GD 6 (systolic blood pressure, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 ± 0.29 mg versus 1.11 ± 0.18 mg, P < 0.01), but barely affected blood pressure or proteinuria of virgin rats compared with those of saline-treated pregnant rats. This was accompanied with adverse pregnancy outcomes including fetal growth restriction. The expression of TLR4 and NF-κB p65 were both increased in the placenta but not the kidney from LPS-treated pregnant rats, with deficient trophoblast invasion and spiral artery remodeling. Furthermore, the levels of inflammatory cytokines were elevated systemically and locally in the placenta from pregnant rats treated with LPS. TLR4 signaling in the placenta was activated, to which that in the placenta of humans with preeclampsia changed similarly. In conclusion, LPS administration to pregnant rats in early pregnancy could elicit TLR4-mediated immune response at the maternal-fetal interface contributing to poor early placentation that may culminate in the preeclampsia-like syndrome.
authors: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
authors: Pingping
authors: P
authors: Xue
authors: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Mingming
authors: M
authors: Zheng
authors: Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors: Ping
authors: P
authors: Gong
authors: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
authors: Caimei
authors: C
authors: Lin
authors: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Jianjun
authors: J
authors: Zhou
authors: Southeast University Medical School, Nanjing, China.
authors: Yujing
authors: Y
authors: Li
authors: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
authors: Li
authors: L
authors: Shen
authors: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Zhenyu
authors: Z
authors: Diao
authors: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Guijun
authors: G
authors: Yan
authors: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Haixiang
authors: H
authors: Sun
authors: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
authors: Yali
authors: Y
authors: Hu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005333:Fetus; D005786:Gene Expression Regulation; D006801:Humans; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D010929:Placentation / Q000187:drug effects; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D051996:Transcription Factor RelA / Q000819:agonists / Q000235:genetics / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA