Introduction: Embryonic diapause is a period of developmental arrest in which the embryo is maintained in a dormant state for an extended period of time. Over 130 species of mammals undergo embryonic diapause, but the molecular control mechanisms remain unknown. In this study, we investigated the potential role of polyamines during embryonic diapause in the mouse. Polyamines play essential roles in cell growth and proliferation, and the regulation of their expression is controlled by the rate limiting enzyme, ornithine decarboxylase (ODC1). In the mink, inhibition of ODC1 with difluormethylornithine (DFMO) induces a reversible arrest in embryonic development.
Materials and methods: To characterise the effect of ODC1 inhibition on mouse embryo development, pregnant mice were treated with DFMO from dpc 4 to 7 and autopsied on dpc 8. The uteri were flushed and the non-implanted blastocysts cultured in vitro. Expression of the polyamine pathway and implantation-related factors were examined in the uterus.
Results and discussion: In 78% of females, we observed no signs of implantation whilst the remaining females exhibited disrupted placental formation and degenerate embryos. From the non-implanted females we obtained viable blastocysts that had limited cell proliferation, but which were able to reactivate when cultured in vitro. Hence, ODC1 inhibition induces a diapause-like state in mouse embryos. Previously, SAMDC has been shown to be able to compensate for a lack of ODC1. To date, we have observed no evidence for compensatory effects. Hence, these results suggest that embryonic diapause is caused by the paucity of polyamines necessary for activation of the embryo.
02 - 04 Sep 2014
World Congress of Reproductive Biology