Gene expression in the developing embryo and fetus.

Determining the stage- and tissue-specific patterns of gene expression shown by the embryo and fetus will provide information about the control of normal development. Identification of alterations in these patterns associated with specific abnormal phenotypes will also be informative regarding the underlying molecular mechanisms. In addition, qualitative and quantitative changes in gene expression that deviate from the norm may provide a potential marker system for predicting future developmental defects, a system that would be particularly useful in preimplantation embryo technologies before recipient transfer. However, there are a number of important issues regarding the interpretation and relevance of many gene expression studies currently undertaken that are often not considered or are ignored. Even when rigorous methodology is applied to detect differences in gene expression, their functional significance is rarely defined. This review discusses the relevance of gene expression changes as diagnostic markers in relation to protein and epigenetic changes and indicates that gene expression studies should be rigorously designed and interpreted to yield meaningful results.

Improving the safety of embryo technologies: possible role of genomic imprinting.

Although developments in mammalian in vitro embryo technologies have allowed many new clinical and agricultural achievements, their application has been hindered by limitations in the developmental potential of resulting embryos. Low efficiencies of development to the pre-implantation blastocyst stage have been consistently observed in most species, including humans, rabbits, pigs and ruminants. Furthermore, in cattle and sheep a wide range of congenital abnormalities currently termed "Large Offspring syndrome" (LOS) are commonly observed as a result of several embryo culture and manipulation procedures. This paper reviews the hypothesis that at least some of the problems associated with embryo technologies may result from disruptions in imprinted genes. Several imprinted genes (i.e. genes which express only the maternal or paternal allele) are known to have significant effects on fetal size and survival in other species and are possible candidates for involvement in livestock LOS. Major changes in putative imprinting mechanisms such as DNA methylation of imprinted genes occur in the mouse embryo during pre-implantation development. Alterations in DNA methylation are stabley transmitted through repeated cell cycles such that changes in the embryo may still act at the fetal stages. Thus any disruption in establishment and/or maintenance of imprinting during the vulnerable periods of embryo culture or manipulation is a plausible candidate mechanism for inducing fetal loss and Large Offspring Syndrome. Identification of these disruptions may provide crucial means to improve the success of current procedures.