Contragestational effects of DL-alpha-difluoro-methylornithine, an irreversible inhibitor of ornithine decarboxylase, in the hamster.

In the hamster, there are remarkable changes in ODC activity in various uterine reproductive tissues during gestation. When DL-alpha-difluoromethylornithine (DFMO), a highly selective irreversible inhibitor of ODC, is given during the early post-implantation period, when ODC activity in the conceptus is rapidly rising and reaches its highest values, it causes pregnancy arrest. Low doses of DFMO are contragestational only during a short period of gestation (day 7 and 8), with primary action on the embryo. Higher doses given soon after implantation (day 5) induce early pregnancy termination by a primary effect on decidual tissue. Biochemical investigations in animals treated on day 5 or day 7 showed that DFMO induces a rapid and dramatic fall in ODC activity in the products of conception. These findings strengthen and extend previous evidence that ODC and polyamines play an essential role in the maintenance of early pregnancy in rodents.