The production of unusually large offspring following embryo manipulation: Concepts and challenges

Embryo culture, nuclear transfer and asynchronous embryo transfer are procedures that can result in the birth of larger than normal offspring. Some birthweights fall well outside the upper limit of the normal population although a minority of offspring is usually affected. Adult liveweights appear not to be affected and the birthweight trait appears not to be heritable although definitive studies have not been reported. Preliminary evidence indicates that cell lineage differentiation in the manipulated embryo is altered resulting in preferential allocation of cells to the trophectoderm. Consequently, a larger than normal placenta develops resulting in aberrant fetal growth and development. It is postulated that this disturbance results from environmentally-induced changes in the regulation of early gene expression. Disruptions to nucleocytoplasmic interactions and to maternal - embryonic signalling are implicated in the phenomenon. The production of large offspring after embryo manipulation casts new perspectives on the roles of reproductive technology in both livestock and human reproduction. However, an understanding of the underlying cellular mechanisms should lead to improved procedures for the handling and manipulation of embryos.