Rhesus monkey clone born with placenta transplant – 01/16/2024 – Science

Chinese researchers used an unusual procedure — a type of placenta transplant — to carry out the first successful cloning of a rhesus monkey (mulatto macaque), a primate widely used in biomedical research around the world. The advance could become an important tool for studies on reproductive and developmental biology, due to the evolutionary proximity between rhesus and humans.

Led by Falong Lu, Zhen Liu and Qiang Sun, all linked to different bodies of the Chinese Academy of Sciences, the work has just been published in the open access specialized journal Nature Communications.

This is not the first successful reproductive cloning of a primate like us — primacy, in this case, goes to the genetic copy of a cynomolgus (Macaca fascicularis), another monkey of Asian origin used as a guinea pig in biomedical and behavioral research.

Another rhesus monkey clone had also been generated before, but the baby only survived a few hours after birth. The Chinese study is the first to produce a cloned member of the species that has survived in long-term health — a male who was 2 years old when the study was accepted for publication in November 2023.

Furthermore, the focus of the study was to refine reproductive cloning techniques and understand why so many things can go wrong during the process — something that has been a constant in this technology since the pioneering birth of Dolly the sheep, in Scotland, in the 1990s.

In fact, in general, it takes hundreds of eggs and dozens of “surrogate mothers” into which to implant embryos to reach a handful of live births, regardless of the species. In most mammal species, the success rate is between 1% and 3%, except in the case of bovids (the cow group), where the numbers are better (from 5% to 20%).

This difficulty is closely related to the molecular reprogramming that cells undergo during cloning. In this process, it is necessary to “convince” the genetic material contained in the nucleus of an adult cell that it has returned to the state that existed at the time of fertilization, when the DNA of the egg and sperm came together.

In normal fertilization, there is, among other things, an intricate programming of activation and deactivation of different sections of DNA. Some of these regions of genetic material are “on” or “off” taking into account, for example, their origin — whether they derive from the father or the mother.

It’s as if there were a label on one of the copies of a gene saying: “Maternal version of the gene. Please only use the paternal version” (in fact, the “tags” are small molecules that prevent that stretch of DNA from being read by the cell) .

In a series of experiments, Chinese researchers confirmed that one of the main problems behind the low efficiency of cloning procedures is the fact that the “tagging” of the clone’s DNA follows messy patterns, different from those of normal fertilization.

And these problems are especially acute in the case of the clone cells that will give rise to the placenta, essential for the circulation of nutrients between the mother and the fetus. As a result, the placenta of the clones develops abnormally, affecting the viability of those embryos and the health of the puppies that are born.

To try to address these limitations, the team produced rhesus monkey embryos through “normal” in vitro fertilization and, at the same time, cloned embryos. Then, using microsurgery techniques, they managed to unite the placental precursor cells of embryos from natural fertilizations with the “body” of cloned embryos. This even caused male clones to have placentas with DNA from non-cloned female individuals.

Although the efficiency of the procedure using this approach is not yet high, more or less on par with traditional cloning methods, Chinese researchers are betting that “transplantation” could facilitate the process in primates in the future.