FAPESP Week London

By André Julião, in London  |  Agência FAPESP – Scientists in Brazil are beginning to understand some of the mechanisms that can lead to greater efficiency in cloning cattle – an important step in increasing productivity in livestock breeding. Researchers have found factors that determine whether or not a cloned embryo has the potential to develop and that indicate whether or not gestation will be successful.   

The rate of embryo production through cloning varies from 35% to 40%, deemed satisfactory and close to the success rates for in vitro-generated embryos. However, only a small fraction of gestations involving cloned embryos result in the birth of calves.  

Increasing this rate would be one way to generate more productive animals. The study was presented during FAPESP Week London, held February 11-12, 2019. 

Since the 1996 birth of Dolly the sheep – the first mammal cloned from an adult somatic cell – cloning has changed considerably. In the case of cattle, however, the efficiency of the technique does not allow it to be used on a large scale.

“When I began doing cloning in the late 1990s and early 2000s, the production rate of embryos from cloning was very low, around 3% to 7%. Today it is compatible with and sometimes even better than in vitro fertilization. The gestation rate is also satisfactory, between 25% and 50%. But pregnancy loss is still very high. In a series of studies conducted for the private sector through 2008, we found that only 53 of the nearly 2,000 embryos we transferred to cows resulted in calves,” said Flávio Vieira Meirelles (photo), a professor in the School of Animal Science and Food Engineering at the University of São Paulo (FZEA-USP).

Meirelles is studying ways to improve success rates for births through cloning in a project funded by FAPESP under an agreement with the Biotechnological and Biological Sciences Research Council of the United Kingdom.

The key to achieving expected results is in the discovery of microvesicles present in somatic cells inside the follicle, whose reproductive cargo is the oocyte [female germinative cell] that gives rise to the ovum. 

“Within these microvesicles are factors associated with reprogramming the oocyte that will control the epigenetic part of the cell [involved in gene activation of silencing through biochemical processes]. This is one way the oocyte acquires the ability to become a cell capable of reprogramming other cells,” he said. 

These microvesicles can also be detected in the blood of a cow carrying a cloned embryo in the early stages of gestation. By analyzing the microRNAs present in the microvesicles, it is possible to determine whether or not the pregnancy will go full term.

“We need to know what is happening to increase the quality of the embryo and thus, improve the number of healthy individuals born,” he said.  

Understanding this mechanism will pave the way for clone embryos to be as efficient as those generated through in vitro fertilization. From then on, cloning on a larger scale will be possible. Current problems result from the fact that just a few reproducers are generated through cloning, which has a high cost. 

“Unlike birds and pigs, which have numerous descendants and short gestation periods, a cow gives birth to only one calf at a time. And the time between gestations is three to five years. This has an influence on how new population will be generated. Using reproductive biotechnology to generate population on a consistent basis will allow us to overcome these challenges,” he said.  

Photo credit: André Julião/ Agência FAPESP