Aspirin and other anti-inflammatory drugs given to newborn rats change their sexual behaviour later in life. The drugs interfere with the brain’s sex-specific development, suggesting that they may also affect equivalent mechanisms in humans.

In theory, mothers taking so-called non-steroidal anti-inflammatory drugs (NSAIDs) might pass on high levels to their baby via the placenta. The list of NSAIDs includes paracetamol (tylenol), aspirin and indomethacin (indocin), which prevents premature labour.

But the researchers caution that, until similar effects have been found in people, expectant mothers should not change their use of medication.

“I don’t want to panic pregnant women,” says Margaret McCarthy, who carried out the study at the University of Maryland, Baltimore, US, with her colleague Stuart Amateau. She says women are already advised to avoid taking unnecessary drugs.

“I don’t think we can say anything about humans based on this,” says Melissa Hines an expert in the neural basis of sexual behaviour at City University in London, UK. She points out that hormonal changes associated with maternal stress in rats have been linked to changes in the sexual behaviour of their offspring - but the same changes do not happen in humans.

Black box

The work is also a significant advance in the fundamental understanding of how testosterone masculinises the brain, says Marc Breedlove, a neuroscientist at Michigan State University in East Lansing, US. “What steroids do is currently something of a black box,” he says.

In particular, McCarthy and Amateau identified a signalling molecule that links the testosterone signal - telling the brain to “be a man” - to changes in the brain.

The discovery of the molecule, called prostaglandin-E2 (PGE2), was a surprise because prostaglandins are usually associated with pain mediation and the body’s inflammatory response. “There was no indication that they were involved in brain development or sex specific effects,” says McCarthy.

Lowered libido

McCarthy and Amateau injected newborn male and female rats with either indomethicin, a powerful blocker of PGE2 production, or PGE2 itself. Male rats given indomethicin had a much lower libido than those given a placebo when they were presented with females as adults.

The research team also found changes in a region of the brain called the preoptic area, which is implicated in both male and female sexual behaviour. The neurons had fewer connections to other nerve cells.

In contrast, females given PGE2 behaved more like males as adults. They were more likely than control rats to mount and attempt to copulate with other females. But the researchers stress that their experiments did not give the rats a choice between the sexes and so do not have implications for sexual orientation.

McCarthy says the next step will be to carry out similar experiments with primates. If the results are similar then it is much more likely that humans will be affected in the same way.

Also, a long-term epidemiological study of 15,000 mothers and their children, based in Bristol, UK, may be able to detect the effect in humans.