Timing and dependence upon mitogen-activated protein kinase signaling for pro-developmental actions of insulin-like growth factor 1 on the preimplantation bovine embryo

Insulin like growth factor-1 (IGF1) increases the proportion of embryos that develop to the blastocyst stage. The objective of the present study was to determine whether the pro-developmental actions of IGF1 are exerted before or after Day 4 of development (i.e., on events occurring through the period of genomic activation versus events coincident with compaction and blastocoel formation) and whether mitogen-activated protein kinase (MAPK) signaling pathways mediate effects of IGF1. Treatment with IGF1 increased the proportion becoming blastocysts at concentrations of 10, 100 and 200 ng/mL, with 100 ng/mL being more effective than 10 or 200 ng/mL. At Day 8, the percent of oocytes that became blastocysts was 30, 34, 43, and 36%, respectively (SEM = 2.6). As compared to controls (30.4%), IGF1 increased the percent of oocytes that were blastocysts at Day 8 when added from Days 4 to 8 (42%) or Days 0 to 8 post-insemination (40%) but there was no significant effect when IGF1 was added from Days 0 to 4 (37%; SEM = 2.2). Actions of IGF1 to increase blastocyst development were reduced when embryos were co-treated with the MAPK inhibitor PD98059. The percentage of oocytes becoming a blastocyst at Day 8 was 21 versus 37% for 0 and 100 ng/mL in the absence of inhibitor and 24 versus 29% in the presence of inhibitor (IGF1 × inhibitor interaction, P < 0.05; pooled SEM = 1.3). In conclusion, IGF1 promotes development to the blastocyst stage by regulating MAPK-dependent events at Day 4 or later of development.