Are male eggs and female sperm on the horizon?
02 February 2008
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Peter Aldhous

"FEMALE sperm", "male eggs" and "same-sex reproduction" - whether these terms fill you with hope or disgust, a reproductive revolution is already in progress. In a handful of labs across the world, biologists are trying to make genetically male cells develop into eggs, and female cells into sperm. If successful, their efforts might one day allow lesbian and gay couples to have children that are genetically their own.

Now Greg Aharonian, a patent analyst from San Francisco, is trying to patent the technologies that could make this possible. In part, Aharonian's goal is to stimulate debate. He argues that lesbians and gay men have a right to know about developments in biology that could allow same-sex reproduction. Aharonian also wants to undermine the argument that marriage should remain an exclusively heterosexual institution because its main purpose is procreation. "I'm a troublemaker," he admits.

In the US, where reproductive clinics are largely unregulated and religious conservatives are at war with gay rights campaigners over same-sex marriage, it should indeed cause controversy. Same-sex reproduction is also an issue in the UK, where Parliament is debating whether in principle to allow IVF using sperm or eggs grown in the lab - although this would only apply to sperm from male cells, and eggs from female cells (see "Gay couples left out").

Aharonian has not shown that the techniques he describes will actually work - that is not necessary to claim ownership of an invention. In his application, Aharonian discusses methods including the use of artificial chromosomes and cellular "reprogramming" techniques. Still, biologists want to see hard experimental evidence. "He claims things that could be possible, but it needs experiments," says Karim Nayernia, a stem cell biologist at Newcastle University in the UK.

Nayernia is working on lab techniques to make sperm from human stem cells. In April last year, he made headlines by taking bone marrow stem cells from adult men and making them develop into spermatogonia - cells that can give rise to immature sperm through a process called meiosis. Since then, Nayernia claims to have repeated the feat for female bone marrow, opening the door for the creation of female sperm.

In so far unpublished work, Nayernia also claims to have made lab-grown male spermatogonia enter meiosis by culturing them with Sertoli cells - support cells from the testes that nurture developing sperm. He has not yet succeeded in getting his female cells to do the same but remains optimistic. "I think, in principle, it will be scientifically possible," Nayernia says, although there will be additional challenges along the way (see "Men not essential?").

Male eggs might not be so hard to make, though. A Brazilian team led by Irina Kerkis of the Butantan Institute in Saõ Paulo claims to have made both sperm and eggs from cultures of male mouse embryonic stem cells (Cloning and Stem Cells, DOI: 10.1089/clo.2007.0031). The researchers have not yet shown that their male eggs can be fertilised to produce viable offspring, but they are thinking about possibilities for same-sex human reproduction.

"We are starting experiments with human embryonic stem cells," says Kerkis. If these are successful, then the next step will be to see if male eggs could be made from cells known as "induced pluripotent stem cells". These seem to behave just like embryonic stem cells, and can be made from adult skin cells using a genetic reprogramming technique pioneered by Shinya Yamanaka of Kyoto University in Japan (New Scientist, 24 November 2007, p 7).

If all these experiments pan out, then the stage would be set for a gay man to donate skin cells that could be used to make eggs, which could then be fertilised by his partner's sperm and placed into the uterus of a surrogate mother. "I think it is possible," says Kerkis, "but I don't know how people will look at this ethically."

Safety is another worry, especially given concerns that Yamanaka's reprogramming technique might make cells prone to becoming cancerous. Safety fears are also likely to surround female sperm, especially if they are created with the help of artificial chromosomes, as Aharonian suggests. "This looks like a very extreme kind of biological manipulation," says Marcy Darnovsky of the Center for Genetics and Society in Oakland, California.

Even if the safety issues could be resolved, same-sex reproduction would remain politically controversial. Religious conservative groups already oppose gay and lesbian adoption, claiming that children are best raised by a mother and a father. And while such groups have used the link between marriage and procreation to argue that homosexuals should not be allowed to wed, techniques that allow gay and lesbian couples to have their own biological children are unlikely to shift their position.

"To the extent that there might be a right to reproduce, it would apply only to natural reproduction," argues Peter Sprigg, vice-president for policy with the Family Research Council in Washington DC, a leading religious conservative group.

Miriam Yeung, until recently director of public policy and government relations with the Lesbian, Gay, Bisexual and Transgender Community Center in New York, predicts a mixed reaction among homosexuals: some may be concerned about safety, others put off by the likely cost, while others are content to have children using donated eggs or sperm. "But there may be some in the community who really want this," she says.

Debra Mathews, a bioethicist at the Johns Hopkins School of Medicine in Baltimore, Maryland, agrees. She is a member of the Hinxton Group, an international consortium on stem cell ethics, which in April is organising a meeting near Cambridge, UK, to discuss issues raised by efforts to grow sperm and eggs in the lab - including the likely demand from homosexual couples. "People want children, and no one wants anyone else to tell them that they can't have them," Mathews observes.

Gay couples left out
In the UK, at least, same-sex reproduction seems likely to be ruled out for the moment. The UK parliament is now debating changes to the 1990 Human Fertilisation and Embryology Act, and the government is under pressure to include an amendment that would allow the future use in IVF of eggs and sperm grown in the lab from stem cells. But supporters of the proposed amendment say that this would only be used to help infertile men produce sperm and infertile women make eggs - it would exclude same-sex reproduction.

"Part of it is pragmatic," says Evan Harris, science spokesman for the Liberal Democrats and one of the amendment's main backers. "This is much more likely to be acceptable to Parliament." But he also argues that the science behind using lab-grown sperm or eggs to help infertile heterosexual couples looks much more promising than efforts to create female sperm or male eggs.

The technology for same-sex reproduction may be at an earlier stage, but one of the government's concerns is that, by excluding homosexual couples, the amendment might be open to challenge under human rights law.

Men not essential?
Creating sperm from women may not be impossible - but there are still some formidable obstacles to overcome.

Most obvious is the lack of a male Y chromosome - which may contain genes necessary for sperm formation, and without which all offspring would be female. One way of overcoming this would be to add "artificial chromosomes" bearing genes from the Y chromosome, suggests Greg Aharonian in his patent application.

He also suggests a kind of "surrogate fatherhood", in which maturing female sperm would be incubated in the testes of a male volunteer to ensure that they gain the correct "imprinting" - chemical alterations to DNA that modify the activity of genes in a developing embryo according to whether they came from the sperm or the egg.

Nevertheless, some biologists feel that the obstacles to making female sperm are huge. "I think it will take far more than 10 years," says Robin Lovell-Badge of the National Institute for Medical Research in London.

Another key problem relates to a phenomenon called "X inactivation", in which one of the two X chromosomes in each of a woman's cells is usually silenced. In the germ cells that give rise to eggs, it reactivates. The same will happen in female cells that become spermatogonia, the germ cells that form sperm, says Lovell-Badge. And this, he argues, will block sperm formation at an early stage.