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17 July 2006
Sperm From Stem Cells: Don't Worry Boys, Your Time's Not Up... Yet
by Serena Mackesy

A story doing the rounds in the UK at the moment tells of how the celebratedly right-on London Borough of Hackney (LBH) recently received a demand from local Wimmin's groups that they establish a women-only graveyard within their bounds. Being the LBH, the council did, in fact, debate the possibility for a bit. But in the end, and possibly because graveyard space has become scarce on our small island over the last few years as local councils flog them off to real-estate developers, they felt that it wasn't really a request they could accede to. "The Council feels," said a statement by one of the committee after the announcement had been made, "that, given the dead status of the residents, it might be possible at that point to let bygones be bygones."

Anyway, the separatist utopia moved a little closer this week, with the announcement that scientists at the Institute for Stem Cell Biology and Regenerative Medicine in Newcastle, UK, had produced a litter of IVF mice using only cultivated mouse-embryo stem cells as the, um, fertilizing agent. Okay, they weren't very good mice, as mice go - they suffered from a variety of physical problems from obesity to malformed limbs, as per the greatly over-hyped cloned sheep experiments - but mice they were nonetheless, produced sans sperm.

It's a bit like old-fashioned breadmaking, in theory at least, where a chunk of the leaven is kept back to start off the next batch. As long as you've got access to a bunch of blastocysts, and an electron microscope and a very, very small syringe, you don't need to bother with the male of the species and their evil wimmin-dominating practices at all. All hail the brave new world! Female fetuses all round!

Well, yes. All very well and good, and frankly, any development that will get the antediluvian hard-line religious bigots in the Bush Administration frothing at the mouth seems like a pretty good thing to me. Obviously, this is an amazing achievement, and hats-off to Professor Karim Nayernia and his big-brain team, but we're not facing a future where a handful of the male of the species are bred to be kept in zoos as antiquarian curiosities just yet.

For a start, the cells produced were quite a long way from being actual sperm: they were gametes, which are actually the interim stage between your spermatogonial stem cell and your mature, wriggly, swimmy little tadpole things. And the intent of the experiment, aside from being part of the greater investigation into nuclear transfer, or therapeutic cloning, which aims to provide tailor-made stem cells to aid disease therapy, was actually to investigate spermatogenesis - the production and development of the male reproductive cell - with a view to aiding male infertility problems. Some of our brothers have difficulty in getting their sperm to mature beyond this stage, and it causes as much heartbreak as any number of blocked fallopian tubes. If anything, this is a wonderful breakthrough in our understanding of general human fertility issues, and that can only be a good thing.

When all's going well, the internal working of the testis (one of the testes) goes roughly like this: a testis contains a (large) number of germ cells called spermatogonia, which contain an entire batch of its producer's human genetic content. The spermatogonia are constantly going through a process of mitosis, or, roughly speaking, cloning. This is why men, the lucky things, always have the same number, where women spit at least one ovum out with every monthly cycle until we run out. Half the mitosed spermatogonia then go through a process of meiosis, during which each cell splits twice. Second time around, it splits its genetic content between the two cells so that ultimately we get four cells, each of which contain half of the human genetic information. These cells are at this point still simple round cells. And here comes the miraculous bit. These cells then mature, developing a "head" where all this genetic information is stored, mitochondria in the middle section which effectively produce the energy needed for movement and a flagellum - the tail part - which makes that movement possible, while still remaining a single cell. So far, only the stages of maturation have been achieved in vitro. So the holy grail of an actual fully-functional test-tube sperm is still some way off. What's been done by the Newcastle team is the combining of the genetic information contained in two separate cells to produce a living, if deeply faulty, creature. Miraculous, but hardly far enough down the line to make men redundant.

Furthermore, any thought that these mice were produced without the help of the male is probably thoroughly erroneous. Though I can't actually find any reference in reports of the breakthrough as to the gender of the blastocysts involved, I'd lay good money on the fact that they were male. Why? Because one of the most commonly touted-about misconceptions of the modern age is that all fetuses are female. They're not. Ova are female and carry the XX chromosome. Sperm are male and carry the XY chromosome. So the sperm is the deciding factor in the fetus's gender. It was previously thought that the "default" phenotype for a fetus without the testosterone input that the Y chromosome carries with it was female, but recent research suggests that there are triggers for the development of "femaleness" as well as "maleness" in fetal development. True, we don't start developing gender differentiations until our sixth week of development, but on a chromosomal level, we're gendered from the moment of conception. So even a blastocyst - which is just a cluster of cells a few days into splitting - is a potential boy or girl blastocyst. My money's on the likelihood that you could prod a girl cell for a thousand years and it would never develop a Y chromosome without someone snipping something away.

So, look, boys, you can stop panicking for now. What's actually happened is this: some very bright scientists have made another step forward in our understanding of the human (well, mouse) body at a cellular level. They didn't find incipient sperm cells and bring them to fruition, as it were; they isolated a bunch of multipotent adult germline stem cells and "switched them on" to become heart, muscle, brain and other cells, among which were spermatagonial stem cells. It's been done before. What's different this time is that, instead of it being shown that germ cells can give rise to cells which resemble gametes, the gametes can actually work, as well. But it's going to be a while before the wimmin separatists of Hackney can hope for a future of peaceful estrogen-only graveyards.

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