Two decades ago, cloning Dolly the sheep in Scotland was a success. However, gene expression in developing clones is abetting heavy failure, according to a new study.

In Dolly's cloning, "somatic cell nuclear transfer" was used wherein a nucleus of an adult cell is transferred to an egg that is unfertilized with its nucleus removed. The cell growth starts after administering it with an electric shock.

This is followed by embryo transfer to mothers who carry the clones to birth. Despite being an important technology, the success rate of cloning in cows has been less than 10 percent.

The bulk of the losses came from embryonic death stemming from failed implantation or a defective placenta, notes the study.

RNA Sequencing Highlights Problems

The study, published in the journal, Proceedings of the National Academy of Sciences makes an effort to address the fundamental questions in cloning failure.

Researchers led by Harris Lewin, a professor at the University of California's Department of Evolution and Ecology and French colleagues resorted to RNA sequencing to unlock the gene expression in cloned cows during implantation.

This was to get a better understanding of the molecular mechanisms that underlie the higher rate of failed pregnancy.

Olivier Sandra, the team leader for the study from the French organization the Institut National de la Recherche Agronomique, said their study offers insights on implantation that drive the progression of pregnancy.

Abnormal Gene Expression

RNA sequencing by researchers revealed that abnormal expression of multiple genes was at the root of the high death rate for embryos cloned. Others factors were botched implantation in the uterus and aborted development of the normal placenta.

The results reiterated that large losses of cloned cows before implantation are borne by problems with critical developmental genes in the extraembryonic tissue.

Since the study was analyzing the extraembryonic tissue of the cloned cows for anomalous expression of more than 5,000 genes, the researchers wanted to show the specifics by comparing their data with the global database of Mouse Genomic Informatics Knockout database.

After comparing with MGI, they documented 123 genes as having a functional annotation of abnormal extraembryonic tissue morphology, 121 with the damage of embryonic lethality and 14 genes having disorders relating to abnormal embryo implantation.

MGI as a global database offers integrated genomic and genetic data for reference. It is a well-known tool for analyzing genes, phenotypes, mutant alleles, gene expression and the recombinase.

Other points of failure include asymmetric hormonal signaling between the cloned embryo and the pregnant cow.

First Cloned Cow Gives Birth

Meanwhile, Eve — the first cow in the world to be created by using handmade cloning technology — has given birth to another calf.

Scientist Simon Walton who created Eve said her successful pregnancy has scotched concerns that cloned animals were like Frankenstein. She had her own natural bull calf in August 2015.

He said Eve was naturally joined with a bull when she was 21 months of age. She became pregnant on her very first cycle and fertility went unimpaired. He said the calf is a cracking bull calf as she seemed to have passed on her elite genetics.