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Inhibition of murine embryonic development by alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. 1980

J R Fozard, and M L Part, and N J Prakash, and J Grove

The activities of ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMDC) and the concentrations of putrescine, spermidine and spermine were measured in mouse uterus placenta and foetus during gestation. The prominent post-implantation biochemical changes in the intact uterus were associated mainly with the deciduomata and significant ODC activity was located in the embryo. Administration of the irreversible inhibitor of ODC, alpha-difluoromethylornithine, DFMO, 2% inthe drinking water during days 5-8 of gestation, abolished the inareases in uterine ODC activity, putrescine and spermidine concentrations and enhanced the activity of SAMDC. Treated animals showed no signs of pregnancy when autopsied on day 18. The alterations in deciduomal weight and the changes in uterine DNA, RNA and protein content indicated that decidualization following DFMO took place normaly but that embryonic growth was arrested. Treatment on single days with DFMO, 200 mg/kg every six h, revealed optimal contragestational effects on day 8 which corresponded exactly to the time of the peak in deciduomal ODC activity. Treatment with DFMO at times other than during the vulnerable period of days 5-8 has less prominent effects on gestation. An increase in ODC activity appears to be an essential factor during a short, but critical, period after implantation for continued murine embryonal growth.

UI MeSH Term Description Entries
D008297 Male Males
D009696 Nucleic Acids High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages. Nucleic Acid,Acid, Nucleic,Acids, Nucleic
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D009952 Ornithine An amino acid produced in the urea cycle by the splitting off of urea from arginine. 2,5-Diaminopentanoic Acid,Ornithine Dihydrochloride, (L)-Isomer,Ornithine Hydrochloride, (D)-Isomer,Ornithine Hydrochloride, (DL)-Isomer,Ornithine Hydrochloride, (L)-Isomer,Ornithine Monoacetate, (L)-Isomer,Ornithine Monohydrobromide, (L)-Isomer,Ornithine Monohydrochloride, (D)-Isomer,Ornithine Monohydrochloride, (DL)-Isomer,Ornithine Phosphate (1:1), (L)-Isomer,Ornithine Sulfate (1:1), (L)-Isomer,Ornithine, (D)-Isomer,Ornithine, (DL)-Isomer,Ornithine, (L)-Isomer,2,5 Diaminopentanoic Acid
D011073 Polyamines Amine compounds that consist of carbon chains or rings containing two or more primary amino groups. Polyamine
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002262 Carboxy-Lyases Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1. Carboxy-Lyase,Decarboxylase,Decarboxylases,Carboxy Lyase,Carboxy Lyases
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females

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