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Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy induces TLR4 activation in the placenta contributing to preeclampsia.

Xue P, Zheng M, Gong P, Lin C, Zhou J, Li Y, Shen L, Diao Z, Yan G, Sun H, Hu Y - PLoS ONE (2015)

Bottom Line: Balanced immune responses are essential for the maintenance of successful pregnancy.Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface.This was accompanied with adverse pregnancy outcomes including fetal growth restriction.

View Article: PubMed Central - PubMed

Affiliation: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus

Mean SBP (A) and urinary protein level (B) of each group on different GDs.Pregnant rats + LPS, N = 15; Pregnant rats + Saline, N = 15; Non-pregnant rats + LPS, N = 5. Data are expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. GD 0; #P < 0.05, ##P < 0.01 vs. saline-treated pregnant group on the corresponding GD.
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pone.0124001.g001: Mean SBP (A) and urinary protein level (B) of each group on different GDs.Pregnant rats + LPS, N = 15; Pregnant rats + Saline, N = 15; Non-pregnant rats + LPS, N = 5. Data are expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. GD 0; #P < 0.05, ##P < 0.01 vs. saline-treated pregnant group on the corresponding GD.

Mentions: There were no significant differences in SBP among the three groups before LPS infusion (Fig 1A). After LPS administration to pregnant rats on GD 5, SBP was significantly increased from GD 6 to 18 compared with that of the saline-treated pregnant group on the corresponding GD (GD 6, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and prior to LPS infusion (from GD 3, 113.73 ± 1.39 mmHg to GD 18, 122.53 ± 2.31 mmHg, P < 0.01). However, SBPs of the saline-treated pregnant group and LPS-treated non-pregnant group did not change significantly throughout pregnancy.


Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy induces TLR4 activation in the placenta contributing to preeclampsia.

Xue P, Zheng M, Gong P, Lin C, Zhou J, Li Y, Shen L, Diao Z, Yan G, Sun H, Hu Y - PLoS ONE (2015)

Mean SBP (A) and urinary protein level (B) of each group on different GDs.Pregnant rats + LPS, N = 15; Pregnant rats + Saline, N = 15; Non-pregnant rats + LPS, N = 5. Data are expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. GD 0; #P < 0.05, ##P < 0.01 vs. saline-treated pregnant group on the corresponding GD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390151&req=5

pone.0124001.g001: Mean SBP (A) and urinary protein level (B) of each group on different GDs.Pregnant rats + LPS, N = 15; Pregnant rats + Saline, N = 15; Non-pregnant rats + LPS, N = 5. Data are expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. GD 0; #P < 0.05, ##P < 0.01 vs. saline-treated pregnant group on the corresponding GD.
Mentions: There were no significant differences in SBP among the three groups before LPS infusion (Fig 1A). After LPS administration to pregnant rats on GD 5, SBP was significantly increased from GD 6 to 18 compared with that of the saline-treated pregnant group on the corresponding GD (GD 6, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and prior to LPS infusion (from GD 3, 113.73 ± 1.39 mmHg to GD 18, 122.53 ± 2.31 mmHg, P < 0.01). However, SBPs of the saline-treated pregnant group and LPS-treated non-pregnant group did not change significantly throughout pregnancy.

Bottom Line: Balanced immune responses are essential for the maintenance of successful pregnancy.Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface.This was accompanied with adverse pregnancy outcomes including fetal growth restriction.

View Article: PubMed Central - PubMed

Affiliation: Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.

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.

No MeSH data available.


Related in: MedlinePlus