Using Skin to Treat Infertility

Infertility affects approximately 3.5 million people in the UK. It is an increasing problem due to decreasing sperm counts, the increasing age of first time parents, and an increase in STIs such as chlamydia. However, recent scientific advancements using artificial sperm and eggs might bring us closer to a cure.

Artificial germ cells (cells that can give rise to sexually reproductive cells), have previously been made in mice by reprograming cells and implanting them into mouse testes to develop sperm, or into ovaries to develop eggs. Until recently this could not be replicated using human cells.

Source: Nature

Researchers working together in the UK and Israel have cracked the first step by converting skin cells into stem cells which were then cultured in a dish with chemicals such as growth factors. These chemicals instructed the cells to become gamete precursor cells which have the potential to grow into mature sperm and eggs by implantation into the ovaries or testes of animals; although this has not yet been done.

So is this a viable option? Well, a study published in March this year described how a lab in China created mouse sperm cells from embryonic stem cells, and injected them into eggs. These were then transplanted into host mothers, who produced healthy offspring. Then when old enough the offspring were bred and produced healthy babies of their own.

As promising as this all sounds the labs say they are not yet ready to mature these precursor cells in humans as there are still too many unknowns and many challenges to overcome.

If this therapy was developed, genetically infertile and same sex couples could potentially have children with genetic material from each partner. However, it will be hard to induce male cells to produce the large and complex egg cells. Debra Matthews, a geneticist and bioethicist at Johns Hopkins University, says it is very important that research goes into ensuring correct egg structures are formed before it can be considered being used for human embryos. It might be impossible for female cells to produce sperm as they are ‘XX’ and therefore lack a ‘Y’ chromosome which contains the instructions to build sperm cells.

It is currently illegal in Britain for fertility clinics to use artificial sperm and eggs. However, if this technology was further developed this could change in the future as support from couples hoping to conceive would likely put pressure on the government to re-examine the law.

Jacob Hanna, one of the lead researchers on the team in Israel says that this area of research will be very important in understanding the biology of infertility. They found a crucial gene, SOX17, which plays a key role in the development of human precursor cells. In mice this role is played by SOX2, and differences like these highlight some of the limitations of using model organisms to understand human development.

This technology could revolutionise the field of developmental biology. Scientists hope to use it to unravel the mechanisms behind the development and maturation of sperm and eggs and to understand the difference in development between healthy and infertile individuals.

At present it is difficult for stem cell researchers to obtain egg cells as they must rely on egg donations, which can be a difficult and painful procedure. If it became possible to create skin cell-derived eggs, this could mark a turning point, boosting research in therapies for diseases such as cancer, Parkinson’s and Alzheimer’s.

Another interesting area is looking at epigenetics: the external changes to our DNA that occur as we grow and develop to regulate gene expression. These changes can be caused by lifestyle factors such as smoking, diet and stress and can lead to misregulation of our genes. These changes are completely removed in sperm and egg cells so that the developing embryo has access to its full complement of genes. If scientists could understand how this occurs, it could open the possibility of developing therapies to erase these mutations in adults.

This is a promising area of infertility research but as with any new finding, there are many considerations to take into account before use in humans. Would we be able to tell if mutations had been introduced? Is there an ethical difference between destroying an artificially produced but still viable embryo and destroying a donated embryo to produce stem cells?

In the UK there are a decreasing number of egg and sperm donations and this could be a light in the dark for couples hoping to become parents, while also relieving the egg donor burden.

There is some concern over how this therapy would change our understanding of how sperm and eggs relate to kinship and parenthood; however, we live in an increasingly tolerant society where large numbers of same sex couples already choose to have families, so surely this new therapy wouldn’t stretch our collective imaginations too far.

#EiraMoore #Health #Infertility #StemCells