Insulin-growth factor-I and apoptosis as determinants of preimplantation bovine embryonic development.

摘要

The overall goal of this dissertation was to understand determinants of preimplantation bovine embryonic survival, particularly following heat shock. There were two main areas of focus---the role of insulin-like growth factor-I (IGF-I) as a cytoprotective molecule for the bovine embryo subjected to heat shock and the impact of apoptosis as a determinant of embryonic survival following heat shock as well as a predictor of embryonic potential for continued development. It was demonstrated in several experiments that IGF-I blocked the effects of heat shock on apoptosis, total cell number and blastocyst development. Actions of IGF-I to block heat shock-induced apoptosis required signaling through the phosphatidylinositol 3-kinase pathway while actions to prevent reduction in cell number required signaling through the mitogen activated protein kinase kinase pathway. Moreover, IGF-I was able to block effects of heat shock on blastocyst development independent of its ability to block apoptosis.;A field study was conducted to determine whether administration of bovine somatotropin (bST) to lactating cows during heat stress would enhance first- and second-service pregnancy rates. It was hypothesized that bST would have such effects because it increases IGF-I secretion. However, while bST increased circulating concentrations of IGF-I and milk yield, there was no effect on fertility, probably because fertility-enhancing actions of bST were counteracted by an increase in rectal temperature experienced in bST-treated cows.;While IGF-I protected embryos from heat shock independent of its actions to block apoptosis, results of the final experiment indicated that the degree of apoptosis can be a determinant of embryonic survival. In particular, it was shown that blastocysts at d 7 or 8 post-insemination that had low group 11 caspase activity had higher hatching rates at d 10 than blastocysts with medium or high caspase activity.;Taken together, results establish IGF-I as a cytoprotective factor for the bovine embryo subjected to heat shock and the importance of degree of apoptosis as a determinant of embryonic survival.