Effects of insulin-like growth factors I and II on tumour-necrosis-factor-a-induced apoptosis in early murine embryos

Abstract

The proposition that members of the insulin-like growth factor superfamily act as rescue factors from apoptosis in murine preimplantation embryos was tested. The cytokine tumour necrosis factor α (TNFα) was used to induce apoptosis. Zygotes were cultured for 5 days to the blastocyst stage in the presence or absence of TNFα and in the presence or absence of the insulin-like growth factors, IGF-I or IGF-II. Tumour necrosis factor α significantly increased the percentage of apoptotic cells and reduced the total cell count in Day 5 blastocysts. When IGF-I or IGF-II were added to the culture medium in the presence of TNFα, the cell number and apoptotic dead cell index (DCI) were restored to control values. Insulin-like growth factor-I alone had a greater effect on total cell number than IGF-II alone, but did not significantly decrease the apoptotic DCI. In contrast, IGF-II significantly reduced the number of apoptotic cells. This study shows that IGFs may play a role as apoptotic survival factors in the early mouse embryo.