It may be your brain not your genitals that decides what sex you really are

OUR brains could be hard-wired to be male or female long before we begin to grow testes or ovaries in the womb. This discovery might explain why some people feel trapped in a body that's the wrong sex, and could also lead to tests that reveal the true "brain sex" of babies born with ambiguous genitalia.

Till now, the orthodoxy among developmental biologists has been that embryos develop ovaries and become female unless a gene called SRY on the Y chromosome is switched on. If this gene is active, it makes testes develop instead. This switch is seen as the key event in determining whether a baby is a girl or a boy. Only after the gonads form and flood the body with the appropriate hormones, the theory goes, is the sex of our minds and bodies determined.

But in a study of mice, a team at the University of California, Los Angeles, has now found that males and females show differences in the expression of no fewer than 50 genes well before SRY switches on. "It's the first discovery of genes differentially expressed in the brain," says Eric Vilain, who led the UCLA team. "They may have an impact on the hard-wired development of the brain in terms of sexual differentiation independent of gonadal induction."

Vilain is presenting details of seven of the 50 genes to the annual meeting of the American Society of Human Genetics in Baltimore this week. Three of these genes are dominant in females and four are dominant in males. The next step for Vilain and his team will be to show that the genes in question really do influence brain sexuality - and not just in mice. This is likely to be a much tougher proposition than merely showing there are differences in expression.

But if the findings are confirmed, they could one day yield blood tests that allow doctors to establish the brain sex of babies born with genitalia that share features of both sexes. At present doctors and parents have to guess which gender to assign for surgical "correction".

Robin Lovell Badge of the National Institute for Medical Research in London, who discovered the SRY gene, is already looking at mice with a Y chromosome lacking the SRY gene, to see if their brains and behaviour are in any way male despite their lack of testes. "The growing feeling is that there will be direct effects on the brain, anatomy and behaviour due to X or Y-linked genes," says Lovell Badge. "It's early days yet, but we're pretty sure there are effects on some aspects of aggression and reproductive behaviour independent of gonadal sex."

Andy Coghlan