Women 'carry egg-making stem cells'

The discovery of stem cells in human ovaries means “it may one day be possible to produce an ‘unlimited’ supply of eggs,” according to the Daily Mail.

The discovery was made during animal and laboratory research looking for the existence of ‘oogenial stem cells’ (OSCs). These are specialised cells that scientists thought might develop into ‘oocytes’, which can, in turn, develop into mature eggs or ‘ova’. Research has previously found that OSCs exist in mice, but this study found that female humans possess them too. When these human OSCs were transplanted into mice they were able to develop into oocytes. Further tests using mouse OSCs demonstrated that the oocytes could then be matured and fertilised to form mouse embryos. In all, the results of this study challenge the idea that females are born with all the oocytes that they will ever have, and that no more are created after birth.

This exciting discovery of human OSCs raises questions about whether new fertility treatments could be developed using their unique properties. However, this experimental research is at a very early stage and much further study will be needed before we can understand if it can be safely used to help patients. It should also be noted that there are many reasons why both men and women may experience fertility problems and even if the findings from this study could one day be put into clinical use, it is unclear how many infertile couples would benefit.

Where did the story come from?

The study was carried out by researchers from Massachusetts General Hospital and Harvard Medical School, USA and Saitama Medical University, Japan. It was funded by the US National Institute on Aging, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation and Vincent Memorial Hospital Research Funds. The study was published in the peer-reviewed journal Nature Medicine.

This story was widely covered, appearing in many newspapers and on the BBC. Most of the coverage of the study was accurate. However, while this study obtained egg-producing stem cells from both healthy mice and healthy young women, it has only demonstrated that human OSCs can develop into oocytes in the laboratory and when transplanted into mice. This means the study does not provide evidence on whether these human oocytes were healthy, functioned normally or could be fertilised.
There are many reasons why both men and women may experience fertility problems, and even if the findings from this study were put into clinical use it is unclear how many infertile couples would benefit.

What kind of research was this?

There is a long-standing scientific belief that females are born with all the oocytes (immature eggs or ‘ova’) that they will have, and that after birth no more oocytes are created. However, in recent years some studies using mice have challenged this idea, indicating that types of cells called ‘female germline’ or ‘oogonial stem cells’ (OSCs) can produce further oocytes in living mice. This was a laboratory- and animal-based study aiming to optimise the method of isolating OSCs, and to see if OSCs are also present in humans. Once isolated, the researchers aimed to test their growth properties and function both in the laboratory and in animal-based systems.

Laboratory and animal-based investigation is the ideal way to answer this basic scientific question. Although the researchers did some experiments with human tissue, legal and ethical reasons meant that they could not determine whether the human oocytes that the OSCs produced were functional (could be fertilised to form an embryo). In addition, much more study will be required before these exciting findings can be put to clinical use.

What did the research involve?

Previous research has found that mouse OSCs can be identified by the presence of a certain protein, called Ddx4 on their cell surface. The researchers first optimised a procedure for isolating these cells from mouse ovaries. They then used the same technique to isolate human OSCs from adult human ovaries. The human ovaries were obtained from six women aged between 22 and 33 with a genetic identity disorder who were undergoing sex reassignment. After isolating the OSCs, they tried to grow them in the laboratory.

The researchers then introduced a piece of DNA into the mouse OSCs, which would cause them to glow brightly (fluoresce), so that they could be identified. They introduced the marked OSCs into the ovaries of normal mice. It was then seen if the mouse oocytes they produced were functional.

The researchers then performed further experiments on human OSCs. They determined whether the human OSCs could form oocytes in the laboratory. They then introduced the piece of DNA coding for the fluorescent marker into the human OSCs and transplanted them into mice, to see whether oocytes would be formed.

What were the basic results?

The researchers successfully used their system to isolate OSCs from mouse and human ovaries. The OSCs produced from both these sources could be grown in the laboratory.

The fluorescently-marked mouse OSCs could form oocytes (immature egg cells) when transplanted into the ovaries of normal mice. These fluorescent oocytes could mature and be fertilised to form embryos in the laboratory.

Human OSCs could form oocytes in the laboratory. In addition, after fluorescently-marked human OSCs were mixed with human ovary tissue and transplanted into mice, fluorescently-marked oocytes were formed. For legal and ethical reasons the researchers did not perform further experiments to see whether these human oocytes were functional.

How did the researchers interpret the results?

The researchers conclude that they have identified female germline or oogonial stem cells in humans, and that they have developed a process for isolating them. They say that “clear evidence for the existence of these cells in women may offer new opportunities to expand on and enhance current fertility-preservation strategies”. They note that the human ovarian tissue used in this study was cryopreserved (frozen), and allowed functional OSCs to be obtained. They also say that these findings will allow more detailed study into oogenesis (the egg-forming process) in the laboratory.

Conclusion

In this exciting study, researchers were able to identify and isolate oogenial stem cells (OSCs), also known as female human germline cells. These OSCs could be grown in the laboratory and were able to form oocytes (immature eggs or ‘ova’) under laboratory conditions and when transplanted into mouse ovarian tissue. The researchers also showed that oocytes formed from isolated mouse OSCs could successfully form mouse embryos.

The results of this study, and of previous studies using mice, challenge the idea that females are born with all the oocytes that they will have, and that after birth no more oocytes are created. This challenge to conventional scientific wisdom raises questions over whether the findings could have an impact on fertility-preservation strategies. In future, OSCs could potentially be isolated from ovarian tissue either before or after it is frozen.

However, the research is at a very early stage and much further study is required. It should also be noted that there are several different reasons why both men and women may experience fertility problems. Even if the findings from this study could one day be put into clinical use, it is unclear how many infertile couples would benefit.