Inhibition of placental ornithine decarboxylase by DL-α-difluoro-methyl ornithine causes fetal growth restriction in rat

Makoto Ishida, Yuji Hiramatsu, Hisashi Masuyama, Yasushi Mizutani, Takafumi Kudo

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-α-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate limiting enzyme of polyamine synthesis was administrated to pregnant rats so that we obtained rat fetuses with IUGR. The changes of maternal nutrition, damage of the placenta, and the direct effect of DFMO on the fetus were examined in this IUGR model. Administration of DFMO did not induced changes of maternal nutrition except for triglyceride and the fetal metabolic state. But the placental weight, ODC activity, and DNA in the placenta were decreased significantly. The ODC activity in the total placenta decreased to less than 10% of that of the control. Depression of ODC activity in the placenta may be the major cause of IUGR induced by DFMO administration, and polyamines play important roles to carry pregnancy.

Original languageEnglish
Pages (from-to)1395-1405
Number of pages11
JournalLife Sciences
Volume70
Issue number12
DOIs
Publication statusPublished - Feb 8 2002

Keywords

  • DL-α-difluoromethyl ornithine
  • Intrauterine growth restriction
  • Ornithine decarboxylase
  • Rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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