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Children of three parents?

mitochondria assisted reproduction baby

Children born to three parents

The concept of a child with three parents makes one think of a television series about imbroglios, but the reality is that it is a technique capable of avoiding certain diseases. 

We already saw the importance of certain structures (mitochondria), which reside in the cells of our tissues to generate energy. 

And the importance that this energy has on the correct development of follicles and quality oocytes. 

Another important facet of mitochondria is that they can be used to avoid certain fertility problems related to genetics. This is the case of the so-called “children of three parents”

For many people, this term may sound like a scientific experiment or even cause some rejection. 

However, behind this name lies a revolutionary technique capable of preventing many congenital and fatal diseases, in the offspring of carrier mothers. 

But let's go in parts. 

 

Mom's mitochondria or why I look like my grandmother

When a sperm and an egg meet and fertilization occurs, there is a combination of genetic information. 

 

Mitochondria, which are located in the cytoplasm (the most extensive and liquid part of our cells), also have their own genetic material. It is a different DNA than what is in the nucleus of cells. 

 

This DNA, in addition to being in the cytoplasm instead of the nucleus of cells, is even smaller than nuclear DNA, and only comes from the mother, not from both parents (like nuclear DNA). 

 

This occurs because, when the sperm and the egg come together, only the part of the sperm nucleus manages to penetrate the wall of the egg. The area of cytoplasm of the male cell is outside the new cell, which means that the mitochondria from the male are not passed on to offspring

 

We can say, then, that all the mitochondria we have come exclusively from our mothers. Although they can later be inherited by both the daughters and sons of that mother. 

 

It is important to know that mitochondrial DNA replicates more intensely than nuclear DNA. This makes it more feasible to recover DNA in good condition in deteriorated human remains to carry out kinship studies. 

 

This fact can be very useful to decipher unknowns about origins or family ties, and also to determine where a family's genetic disorder comes from.

 

This mitochondrial DNA, inherited from mother, grandmother and great-grandmother, represents a very small percentage of the total DNA in cells. It is estimated that it supposes less than 1% in mammals.

 

However, as we mentioned in the previous post (link), the ability of an egg to be successfully fertilized is believed to be associated with a woman's mitochondrial health. Correlations have been identified between reduced amounts of this special DNA and infertility, as well as between mitochondrial DNA mutations and fertilization rates.

 

Unfortunately, when mitochondria stop functioning, they cause serious syndromes. Many times incompatible with life. Depending on the location of the mitochondria in the body, there may be dysfunctions in the brain, ears, eyes, muscles... 

 

For many years there has been no hope for the offspring of mothers carrying alterations in mitochondrial DNA. Fortunately, Science has managed to reverse this situation in a creative way.

 

A creative idea to overcome genetic pathologies

In the last decade, advances in therapies to restore mitochondria-related oocyte quality have been enormous. 

 

Until now, therapeutic attempts had focused mainly on: 

 

  • The use of certain nutrients to restore mitochondrial function.
  • The transfer of mitochondria from cells with mitochondrial integrity to oocytes with impaired mitochondria
  • Mitochondrial replacement techniques in women with mutations that cause mitochondrial diseases. 

 

New technologies related to these small organelles had opened new possibilities for therapeutic advances, improving the success rates of IVF in women with compromised oocyte quality.

 

It was in 2016 when another leap was made in this race to overcome genetic irregularities. 

 

The first fruit that this technique bore was born healthy in Mexico, thanks to the work of American doctors, geneticists and Jordanian parents. They had to move to Mexican territory, since work with human embryos was more flexible there. 

 

It was a revolutionary technique that combined the genetic load of a father and a mother with a small amount of the genetic code (mitochondria) of a donor mother. In total, three fathers!

 

The newborn's mother suffered from a rare mitochondrial disease, Leigh syndrome, which is why he had previously lost two children. This syndrome is a fatal genetic pathology that affects the developing nervous system and is transmitted through the mother's DNA, even if she is healthy. This technique turned out to be the only viable option and the process was a complete success. Even today it is not a widespread technique, but it is a great advance for science.

 

The curious thing is that a person's physical traits and behavior are governed by genes encoded in nuclear DNA and not in mitochondrial DNA. In this way, through this technique, there would be no modification of the external characteristics of the newborn. 

 

This mitochondrial DNA does not express hormones, pigments or proteins that make up the tissues or organs of our body, so these children would never look like the donor mother. 

 

On the other hand, mitochondrial DNA does encodes proteins needed by mitochondria, to be able to oxidize nutrients and convert them into energy for the rest of the body. And this is an essential process for every body to function. 

 

For this reason, technicians have equated the result of this technique with an organ transplant (heart, lung, liver, etc.) at a microscopic level, due to the implications it would have if it had not been performed. 

 

Ethical problems: destruction of embryos

An additional aspect that complicated the case of this first birth of a child to three parents was that the parents, from Jordan, professed the Muslim religion and did not want to destroy any embryos in the process. 

 

The 'simplest' thing would have been to fertilize two different eggs (one from the mother and one from the donor) with the father's sperm.

 

Both nuclei of the embryos would be removed and only the one that was the result of the couple's embryo would be preserved. Afterwards, it would be introduced into the embryo of the father and the donor, and it would be ready to be placed in the mother's uterus. In short, it would be about replacing the part of the cell that contains the mother's mitochondrial DNA (pathological) with mitochondrial DNA from another woman, preserving the nuclear DNA of the parents. In this way the baby would be born free of the mother's mitochondrial disease. 

However, in this first case, the couple did not accept the destruction of any of the embryos for religious reasons. So the medical team was forced to further complicate the technique. 

First, the nucleus was removed from the mother's egg and introduced into an egg from the donor (which had previously had its own nucleus removed). In this way, the resulting egg was fertilized with the father's sperm and was introduced into the mother's uterus to develop. 

As almost always, there are defenders and detractors of this technique. 

 

Opponents argue that there is still time to study possible side effects of the “3-parent child” technique in the long term. Both in the newborn and in the subsequent generations that follow, especially if it was a woman. 

 

Defenders, on the other hand, argue that nuclear DNA, the truly determining factor, is not being manipulated and that the procedure has helped women with about 30 children around the world become mothers. 

 

What cannot be denied is that it is a work of reproductive art. For now, successfully. 

 

You should never lose hope of becoming a mother.

 

References:

  • Javier Salas. A baby is born with the new 'three genetic parents' technique. The country. Science/Material 06 OCT 2016
  • The controversial technique by which the first "three-parent baby" was born as a fertility method. BBCNews. April 2019
  • Kara Rogers Three-parent baby. Brittania Medicine. 
  • Mitochondrion, much more than an energy converter. British Society for Cell Biology
  • Jessica Hamzelou. World's first baby born with new 3 parent” technique. News Scientist. September 2016
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