Cow gene study shows why most clones fail

It has been 20 years since Dolly the sheep was successfully cloned in Scotland, but cloning mammals remains a challenge. A new study by researchers from the U. S. and France of gene expression in developing clones now shows why most cloned embryos likely fail. 

Dolly was cloned using the technique of "somatic cell nuclear transfer," when a nucleus from an adult cell is transferred into unfertilized egg that has had its nucleus removed, and is then shocked with electricity to start cell growth. Embryos are then transferred to recipient mothers who carry the clones to birth.

Cloning cattle is an agriculturally important technology and can be used to study mammalian development, but the success rate remains low, with typically fewer than 10 percent of the cloned animals surviving to birth. The majority of losses are due to embryonic death, a failure during the implantation process, or the development of a defective placenta.

In a study published Dec. 8 in the journal Proceedings of the National Academy of Sciences, Harris Lewin, professor in the UC Davis Department of Evolution and Ecology, and colleagues in France and the U. S. used RNA sequencing to look at gene expression in cloned cows during implantation in order to get a better understanding of the molecular mechanisms that lead to a high rate of pregnancy failure for clones.

When they compared the results to the Mouse Genomic Informatics Knockout database they found 123 genes that corresponded with functional annotation of abnormal extra-embryonic tissue morphology, 121 associated with embryonic lethality, and 14 with abnormal embryo implantation.

"Our data confirm that the interactions between the uterus and the extra-embryonic tissues is critical during implantation, making this step a major hurdle for the progression of pregnancy."