Thrombomodulin improves maternal and fetal conditions in an experimental pre-eclampsia rat model

Mihwa Shin, Hirofumi Hino, Midori Tamura, Bunpei Ishizuka, Mamoru Tanaka, Nao Suzuki, Takeshi Tateda

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11 Citations (Scopus)


Aim: The aim of this study was to investigate whether the consecutive administration of recombinant thrombomodulin (r-TM) for 4 days improves maternal and fetal conditions and physiological outcomes in an N'-nitro-L-arginine- methyl ester hydrochloride-induced and low-dose endotoxin-induced pre-eclampsia (PE). Methods: r-TM or saline was administrated i.v. to normal pregnant and experimental PE rats for 4 days. The maternal condition, vascular endothelial growth factor receptor-1 (VEGFR-1), fetal conditions, uteroplacental blood flow (UPBF), and oxygenation in the placenta and fetal brain was evaluated on gestational day 21. Results: Significant increases in the mean arterial blood pressure, VEGFR-1 values and fetal death rate were observed in PE rats compared with control rats, while maternal and fetal bodyweight and fetal brain weight were substantially lower. Hypoperfusion and hypo-oxygenation in both the placenta and fetal brain tissues occurred in PE rats. Although r-TM failed to improve hypertension and affect the differences in maternal bodyweight between the groups, r-TM significantly improved hypoperfusion and fetal and maternal conditions, including VEGFR-1 values (6.5 ± 4.0 vs 2.2 ± 2.7 ng/mL, PE vs PE with r-TM, respectively; P < 0.05). Although not significant, a decrease in the fetal death rate was observed in PE rats administrated r-TM (36.1 ± 17.6% vs 25.0 ± 23.8%, P = 0.077). Conclusion: The severe reductions in the UPBF and the placental oxygenation imply that regional hypoperfusion occurs in association with systemic mean arterial pressure. r-TM may be a candidate medical treatment for PE complications.

Original languageEnglish
Pages (from-to)1226-1234
Number of pages9
JournalJournal of Obstetrics and Gynaecology Research
Issue number5
Publication statusPublished - 2014 May
Externally publishedYes


  • Fetal growth restriction
  • Pre-eclampsia
  • Recombinant thrombomodulin
  • Uteroplacental circulation
  • Vascular endothelial growth factor receptor-1

ASJC Scopus subject areas

  • Obstetrics and Gynaecology


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