Ornithine decarboxylase inhibitors and fetal growth retardation in mice

Putrescine (PUT) and the putrescine analogues, 1,3-diaminopropane (DAP) and 1,6-diaminohexane (DAH), were administered to pregnant female mice during the time of maximal fetal ornithine decarboxylase (ODC) activity, days 10-14 of gestation. Such treatment resulted in an inhibition of fetal ODC activity, as measured 2 hours later, and a proportional decrease in fetal weight, as measured on day 18 of gestation. The order of effectiveness for these compounds was DAP greater than DAH greater than PUT. Neither DAP nor DAH nor PUT were fetocidal nor maternally lethal under the treatment regimen employed. The generality of the effect of these compounds, i.e., the retardation of fetal growth and the lack of gross malformations, is consistent with the hypothesis that they are interfering with a primary process, probably protein synthesis. The restricted time span of effectiveness implies that these compounds are specific inhibitors of ODC and that decreased ODC activity is producing an effect on growth.