PMID- 25853857
OWN - NLM
STAT- MEDLINE
DCOM- 20160323
LR  - 20210929
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy 
      induces TLR4 activation in the placenta contributing to preeclampsia.
PG  - e0124001
LID - 10.1371/journal.pone.0124001 [doi]
LID - e0124001
AB  - 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 mug/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-kappaB 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.
FAU - Xue, Pingping
AU  - Xue P
AD  - Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
FAU - Zheng, Mingming
AU  - Zheng M
AD  - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing 
      University Medical School, Nanjing, China.
FAU - Gong, Ping
AU  - Gong P
AD  - Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western 
      Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Lin, Caimei
AU  - Lin C
AD  - Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
FAU - Zhou, Jianjun
AU  - Zhou J
AD  - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing 
      University Medical School, Nanjing, China.
FAU - Li, Yujing
AU  - Li Y
AD  - Southeast University Medical School, Nanjing, China.
FAU - Shen, Li
AU  - Shen L
AD  - Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
FAU - Diao, Zhenyu
AU  - Diao Z
AD  - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing 
      University Medical School, Nanjing, China.
FAU - Yan, Guijun
AU  - Yan G
AD  - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing 
      University Medical School, Nanjing, China.
FAU - Sun, Haixiang
AU  - Sun H
AD  - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing 
      University Medical School, Nanjing, China.
FAU - Hu, Yali
AU  - Hu Y
AD  - Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150408
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Rela protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factor RelA)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - *Disease Models, Animal
MH  - Embryo Implantation/drug effects
MH  - Female
MH  - Fetal Growth Retardation/physiopathology
MH  - Fetus
MH  - Gene Expression Regulation
MH  - Humans
MH  - Injections, Intravenous
MH  - Lipopolysaccharides/*administration & dosage
MH  - Placenta/blood supply/drug effects/*immunology/physiopathology
MH  - Placentation/drug effects
MH  - Pre-Eclampsia/chemically induced/genetics/*immunology/physiopathology
MH  - Pregnancy
MH  - *Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/agonists/genetics/*immunology
MH  - Transcription Factor RelA/agonists/genetics/immunology
PMC - PMC4390151
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/09 06:00
MHDA- 2016/03/24 06:00
PMCR- 2015/04/08
CRDT- 2015/04/09 06:00
PHST- 2014/12/08 00:00 [received]
PHST- 2015/02/25 00:00 [accepted]
PHST- 2015/04/09 06:00 [entrez]
PHST- 2015/04/09 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
PHST- 2015/04/08 00:00 [pmc-release]
AID - PONE-D-14-53075 [pii]
AID - 10.1371/journal.pone.0124001 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 8;10(4):e0124001. doi: 10.1371/journal.pone.0124001. 
      eCollection 2015.