One study provides information that could be used to treat infertility caused by autosomal or chromosomal sex disorders, but also opens up the possibility of bipaternal reproduction, between two males, in humans.

A Japanese research team has produced oocytes from the cells of male mice and fertilized them, obtaining offspring, as published in the scientific journal Nature.

In this study, researchers have efficiently converted the XY chromosome set to XX in mouse pluripotent stem (PS) cells. To do so, they removed the Y chromosome and subsequently duplicated the X chromosome.

This has been done in both embryonic stem cells and induced pluripotent cells (iPS) obtained from the tail of a sexually mature male mouse.

Subsequently, artificially feminized PS cells have been derived into oocytes, the female gametes, which gave rise to viable and fertile offspring after being fertilized. This offspring is bipaternal, that is, they are children of two male parents, without a mother, although a female was necessary to carry out the gestation.

This is not the first time that bipaternal inheritance has been obtained in mice, as it had already been achieved before, as described in two studies from 2011 and 2018 (see HERE).

The novelty of the current research is that it achieves the sexual conversion of male (XY) to female (XX) stem cells to derive gametes, whereas previous studies used stem cells with a single X chromosome (iPS X0 cells and embryonic stem cells haploid respectively).

This has two important advantages. First, abnormalities in individuals born by the above methods have been avoided, as well as premature death. Secondly, the presence of the two X chromosomes is expected to prevent infertility problems associated with the previous methods.

This study provides information that could be used to treat infertility caused by autosomal or sex chromosomal disorders, but also opens the possibility of bipaternal reproduction between two males in humans.

Katsuhiko Hayashi, lead author of the research, stated at the Third International Summit on Human Genome Editing, held between March 6 and 8, 2023 at the Francis Crick Institute in London, that it would be technically possible to generate human oocytes from male skin cells within a decade.

However, it is an approximation, since it is unknown if the difficulties that the technique entails can be overcomed and sufficient levels of safety are achieved to think about being able to use it in humans.

Antonio Requena, medical director of the Valencian Infertility Institute (IVI) has pointed out to ABC Salud that the use of pluripotent cells for their transformation into oocytes “is difficult due to the complexity of the oocyte (not only because of the transmission of chromosomes, but also because of the complexity of the cytoplasm that will be the support of the future embryo in the first days of development).

In fact, there are already publications on the production of mouse spermatozoa from undifferentiated adult cells, but this technique is easier (within its complexity) because the spermatozoon’s main function is only to provide the genetic load of the male. […] There is still a long way to go».

Bioethical assessment

From a bioethical point of view, this experiment may entail safety risks for the conceived children that are greater than current in vitro fertilization and that are difficult to justify.

Likewise, we believe that reproductive autonomy should not be seen as a moral absolute to which science must respond.

As the Pontifical Academy for Life expressed in its Final Communiqué of the X General Assembly “It should be stressed, however, that a more than understandable and licit “desire for a child” can never be transformed into an arrogant “right to a child” and, moreover, a “right to a child at all costs”. No person can claim the right to the existence of another, otherwise the latter would be placed on a lower level of value than the one who claims such a right”.

Previously, we have published information on the risks that are difficult to control associated with genetic reprogramming techniques, which pose a serious difficulty for their clinical application.

The complexity of the human genome, the lack of knowledge that still prevails about genetic interaction, and the impossibility of predicting the effects associated with the profound modifications involved in cellular reprogramming make it difficult to control the undesirable effects associated with it. Especially when, as in this case, it is a matter of genetically modifying the germ line, the gametes, which implies possible consequences on all the cells of the future organism.

Certainly, cell reprogramming, a promising technique developed by S. Yamanaka (2012 Nobel Prize in Medicine), makes it possible to obtain pluripotent cells from adult cells and avoids the use of human embryos and their destruction. This represents a significant advantage for their bioethical assessment, but the still unresolved safety issues associated with these techniques make it necessary to adopt prudent positions in order to avoid serious and unpredictable future consequences.

The end of sexual reproduction?

The possibility of obtaining offspring from the cells of the same individual or from two individuals of the same sex, as in the case at hand, would mean the end of sexual reproduction as it has evolved in nature. This is what has allowed the improvement of species.

There are two insurmountable difficulties that arise in this regard:

On the one hand, it would make sexual complementarity in reproduction unnecessary, and, therefore, the contribution of male and female contributions to the necessary genetic diversity and balance.

On the other hand, this sexual diversity in the future upbringing of children is also questioned, delving into the models that do without the mother or father when the male and female gametes are obtained by the procedures now proposed.

Although these family models exist today, assisted reproduction techniques continue to use male and female gametes to obtain embryos. Their gestation and upbringing can be in multiple ways, different from a traditional family made up of a father and a mother.


Lucía Gómez Tatay and Julio Tudela

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia


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