by Lisa Carr
Male and female infertility is a great focus for research in the scientific world. Research centering on the direct causes of male fertility has seen some landmark breakthroughs in the last decade, with causes being attributed to both genetic and environmental origins. In 2003, US researchers proposed that environmental lead could be leading to cases of male infertility. The year 2001 saw German scientists linking adeno-associated virus (AAV) to cases of male infertility by examining the semen of men both healthy and infertile men. These are just two cases in the ongoing unraveling of the mysterious condition that is male infertility. The cellular basis of male infertility is due to cells in the testes being unable to divide to provide fully functioning sperm. Alongside all this root cause research, there are constant advances in reversal of this fertility state, focusing on how to create functioning sperm. However, these advances are bound by ethical and legal standards. Concerns over safety and welfare of participants mean that many of these studies have not crossed the threshold into human trials and so far many of the miraculous infertility cures have only been seen in mice subjects.
One of the more recent breakthroughs has seen artificial sperm being used to create viable offspring in the lab environment. A number of healthy mice offspring were created in Chinese labs by fertilising normal mouse eggs with early stage sperm cells created using embryonic stem cells from the mice. Not only is this a landmark achievement for male infertility, this is the latest of a number of breakthroughs in embryonic stem cell therapy developments. To create the sperm cells from the embryonic stem cells, scientists induced a process known as meiosis in the stem cells. From this, early-stage stem cells – round, tailless cells known as spermatids were injected into mouse egg cells. The fertilised embryos were subsequently transferred to females who gave birth to at least six healthy mice. These mice were then able to produce viable children of their own, a second generation of healthy offspring.
This study provides fresh hope in the ongoing research to reverse male fertility. But not only does this pose ethical concerns due to the research needing to be done on infertile males, studies with human embryonic stem cells are similarly wrought with legality with many groups opposing the use of embryonic stem cells in research due to blastocyst’s being destroyed in the process. These are early-stage human embryos and opposition groups often argue that destroying a blastocyst is destroying a potential human life and this debate is ongoing.
Therefore, despite the years of work that has gone into creating artificial sperm for reproductive purposes, it could be a long time before these sorts of studies can be translated to human clinical trials. “Despite years of work, scientists have never managed to pull of the same trick with human stem cells, but the latest study could provide fresh impetus to the effort,” said Jiahao Sha, director of the Laboratory of Reproductive Medicine at Nanjing Medical University in China.
“If it works, human germ cells could possibly be produced. However, in the current stage, ethics should be concerned and any possible risks ruled out.”
Current IVF technologies already face a number of ethical concerns despite this practice being undertaken in many countries around the world. IVF is the process by which eggs are removed from the ovaries of a female and mixed with sperm in a laboratory culture dish. Fertilisation takes place outside the body in a culture dish before the embryo is introduced back into the body. Despite thousands of IVF babies being born since the late 1970’s, many people still claim that the process is wasteful as many fertilised embryos are destroyed and people accuse the process of being ‘unnatural’. Many IVF processes take place with viable sperm and eggs from both parent donors. However, in a case where the male’s sperm aren’t viable, where he is infertile, artificial sperm created by scientists in the lab such as in China could be the next answer.
Many couples aren’t necessarily comfortable with accepting sperm from a male donor, instead wishing that the child has genetic material from both parents. By cultivating artificial sperm from pluripotent stem cells, this might allow many couples to have children who weren’t able to in the past. Infertility affects up to 15% of couples. Males are solely responsible for 20 to 30% of infertility cases.
Fertility clinics in the UK are banned from using artificial sperm or eggs to treat infertile couples – a stark reminder that this is still a sensitive process bound by ethics and legalities. However, if scientists are able to perfect the process of creating sperm from stem cells in a harmless and efficacious manner, MP’s may be forced to revise the existing laws around this practice. Honing in the scientific process further, more promising approaches could use adult skin cells or adult pluripotent stem cells to make viable sperm and eggs – avoiding the ethical concerns surrounding the use of blastocyst embryos.
This has been a major breakthrough in a series of advances in reproductive medicine. But it could still be a long time until this research can be put into practice. Mary Ann Handel, a scientist at the Jackson Laboratory in Maine said: “The implications for managing human infertility are there, but I think they are considerably further off in the future.”