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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 intricacies, but the reality is that it is a technique capable of avoiding certain diseases. 

We have already seen 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. It is the case of the calls “children of three parents”

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

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

But let's go by 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. This is a different DNA from the one 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 spermatozoon and the ovum come together, only the part of the nucleus of the spermatozoon manages to penetrate the wall of the ovum. The area of ​​the cytoplasm of the male cell is left out of the new cell, which means that the mitochondria from the male are not passed on to offspring

 

We can therefore say that all the mitochondria we have come exclusively from our mothers. Although later they can be inherited by both the daughters and the 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 the genetic disorder of a family comes from.

 

This mitochondrial DNA, inherited from the 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 thought to be associated with a woman's mitochondrial health. Correlations have been identified between the reduced amount of this special DNA and infertility, as well as between mitochondrial DNA mutations and fertilization rates.

 

Unfortunately, when mitochondria stop working, 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 mitochondria-related oocyte quality restoration therapies have been enormous. 

 

So far, therapeutic attempts have 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 up new possibilities for therapeutic advances, improving IVF success rates 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 produced by this technique was born healthy in Mexico, thanks to the work of doctors, American 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) from a donor mother. In total, three parents!

 

The newborn's mother suffered from a rare mitochondrial disease, Leigh's syndrome, reason for which he had previously lost two children. This syndrome is a deadly genetic pathology that affects the developing nervous system and is transmitted by the mother's DNA, even if she is healthy. This technique turned out to be the only viable option and the process was very successful. 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 mitochondrial DNA. In this way, through said technique, there would be no modification of the external characteristics of the newborn. 

 

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

 

In contrast, 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, the technicians have equated the result of this technique with an organ transplant (heart, lung, liver, etc.) at a microscopic level, due to the implication that it would have if it had not been carried out. 

 

Ethical issues: destruction of embryos

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

 

The 'simple' 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 embryo of the couple would be kept. Later, it would be introduced into the embryo of the father and the donor, and the mother's uterus would be ready to be placed. In short, it would be a question of replacing the part of the cell that contains the mitochondrial DNA of the mother (pathological), by a mitochondrial DNA from another woman, conserving 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 of the mother's egg was extracted and inserted into a donor egg (which had previously had its own nucleus removed). In this way, the resulting egg was fertilized with the father's sperm and 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 subsequent generations that follow, especially if it had been a woman. 

 

The defenders, on the other hand, argue that the nuclear DNA, the really determining one, is not being manipulated, and that the procedure has helped women with about 30 children around the world to become mothers. 

 

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

 

You should never lose hope of being a mother.

 

References:

  • Javier Salas. A baby is born with the new technique of 'three genetic parents'. The country. Science/Material 06 OCT 2016
  • The controversial technique by which the first "three-parent baby" was born as a fertility method. BBC News. 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