High-dose paracetamol changes brains of male fetuses in mice

The daily use of paracetamol in pregnant mice affects the brain development and behaviour of male offspring, according to researchers in Denmark.

The male pups exposed to high doses of paracetamol during pregnancy were less aggressive and less likely to mate. There were also changes in the region of the brain that controls sex drive. The findings, published in the journal Reproduction, build on previous research showing that paracetamol can inhibit the male sex hormone testosterone.

'We have demonstrated that a reduced level of testosterone means that male characteristics do not develop as they should. This also affects sex drive,' said lead researcher Dr David Møbjerg Kristensen at the University of Copenhagen, Denmark. 'Mice exposed to paracetamol at the fetal stage were simply unable to copulate in the same way as our control animals.'

Researchers gave pregnant mice either plain water or water laced with a standard or high-dose of paracetamol until birth. Male offspring were tested for typical 'masculine mouse behaviours' such as marking territory, aggression and sexual activity. Scientists found that high-dose mice were more passive and unable to copulate. Researchers then examined the structure of the brain.

'The area of the brain that controls sex drive - the sexual dimorphic nucleus - had half as many neurons in the mice that had received paracetamol as the control mice,' explained Professor Anders Hay-Schmidt also at the University of Copenhagen, and first author of the study.

The brain changes were only seen in mice exposed to high doses of paracetamol. The equivalent high-dose in humans would be three-times the maximum dose recommended for adults.

Dr Rod Mitchell at the University of Edinburgh, who was not involved in the study, explained that, though 'well conducted', the study 'does not represent how pregnant women generally take paracetamol, which is typically for a short duration (over 24-48 hours)'.

'It is important to recognise that management of pain and fever during pregnancy are important for the health of mother and baby,' added Dr Mitchell. 'This new study therefore reinforces the current recommendation from the [UK] Department of Health that pregnant women should only use paracetamol for the minimum period necessary to provide symptomatic relief of pain and fever.'