Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat.
The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-alpha-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.
Ishida
Makoto
M
Department of Obstetrics and Gynecology, Okayama University Medical School, Japan.
Hiramatsu
Yuji
Y
Masuyama
Hisashi
H
Mizutani
Yasushi
Y
Kudo
Takafumi
T
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000518:Eflornithine / Q000378:metabolism / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D008297:Male; D009929:Organ Size / Q000187:drug effects; D065108:Ornithine Decarboxylase Inhibitors; D010920:Placenta / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D011247:Pregnancy / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D014280:Triglycerides; D000518:Eflornithine