Inhibition of rat embryonic development by the intrauterine administration of alpha-difluoromethylornithine.
Decarboxylation of L-ornithine by L-ornithine decarboxylase (ODC; E.C.4.1.1.17.) is the initial step in the biosynthesis of putrescine, ODC activity is generally low in most tissues, marked increases are associated with rapid tissue growth and particularly with mammalian embryogenesis. 0.5 mg/kg of DL-alpha-difluoromethylornithine (DFMO) (irreversible inhibitor of ODC) was administered to uterine horns of Long-Evans adult rats during the 4th day of pregnancy. As control material, saline (0.15 M) was administered to contralateral uterine horn. The animals were sacrificed on different days, the uterine horns were removed and the number of implant of implanted embryos were counted. DNA, RNA, protein and dry weight content in implantation sites (5th day of pregnancy) indicated that decidualization following DFMO took place normally but that embryonic growth was arrested in the treated horn. When 100 micrograms of putrescine were added together with DFMO, the embryotoxic effect was absent.
D000818:Animals; D003281:Contraceptives, Postcoital / Q000494:pharmacology*; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D000518:Eflornithine; D010064:Embryo Implantation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011247:Pregnancy; D011700:Putrescine / Q000096:biosynthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D003281:Contraceptives, Postcoital; D003283:Contraceptives, Postcoital, Synthetic; D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D011700:Putrescine; D000518:Eflornithine