Pronuclear Transfer

A Brief History

The first attempted pronuclear transfer procedures were performed on mice in the 1990s, suggesting the possibility of preventing the transmission of mutated mitochondrial DNA. However, it was not until 2003 that scientists at Sun Yat-Sen University in China attempted the procedure with human embryos. Although illegal in the United Kingdom and the United States, five genetically modified embryos were implanted into a woman. She became pregnant with twins after researchers selectively reduced the pregnancy by one fetus. However, after some months, the woman suffered miscarriages and lost both fetuses.

Fast forward to 2008, researchers at Newcastle University released the news that they had successfully transferred pronuclear DNA between very early human embryos. They arrested the embryos’ growth five days later so that the researchers could analyze them. A paper was subsequently published in 2010 that reported that the human embryos developed normally to the blastocyst stage in six to eight days after pronuclear transfer, making the procedure a success in preventing mitochondrial disease.

The Procedure

  1. In vitro fertilization techniques are used to create an embryo with the intended parents’ sperm and egg. The resulting embryo has the mother’s unhealthy mitochondria, found in the cytoplasm of her egg.
  2. At day one of embryonic development, while the embryo is still a single undivided cell, the two pronuclei, or unfused nuclei of the egg and sperm, are removed from the cell for transfer. Removal of the two pronuclei leaves behind almost all of the mother’s unhealthy nuclei. The cell without nuclei is then discarded.
  3. Separately, a second embryo is created from the egg of an unrelated female donor, which has healthy mitochondria, and the intended father’s sperm. While the intended father’s sperm is usually preferred, donor sperm could be used if the intended father’s sperm is not of sufficient quality and to avoid intracytoplasmic sperm injection, ICSI. The second embryo is also enucleated at day one of development.
  4. The intending parents’ pronuclei are then inserted into the second enucleated embryo.
  5. The new embryo now contains the pronuclear DNA of the intended parents and the healthy mitochondria from the female donor’s egg.
  6. The embryo can now be transferred back into the intended mother and can continue to develop unaffected by inherited mitochondrial disease.

Pronuclear Transfer, simplified

Pronuclear transfer is one of two forms of mitochondrial replacement. Learn about another type, called >>Maternal Spindle Transfer or learn more about how these procedures are >>Curing Disease.

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