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Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour

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  • Anders Hay-Schmidt
  • Olivia T Ejlstrup Finkielman
  • Benjamin A H Jensen
  • Christine F Høgsbro
  • Jacob Bak Holm
  • Kristoffer Haurum Johansen
  • Tina Kold Jensen
  • Anderson Martino Andrade
  • Shanna H Swan
  • Carl-Gustaf Bornehag
  • Søren Brunak
  • Bernard Jegou
  • Karsten Kristiansen
  • David Møbjerg Kristensen
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Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.

Original languageEnglish
JournalReproduction (Cambridge, England)
Volume154
Issue number2
Pages (from-to)145-152
Number of pages8
ISSN1470-1626
DOIs
Publication statusPublished - 2017

    Research areas

  • Acetaminophen/toxicity, Aggression/drug effects, Aniline Compounds/toxicity, Animals, Ejaculation/drug effects, Female, Gestational Age, Male, Mice, Inbred C57BL, Neurons/drug effects, Pregnancy, Prenatal Exposure Delayed Effects, Preoptic Area/drug effects, Risk Assessment, Sex Characteristics, Sexual Behavior, Animal/drug effects, Territoriality, Urination/drug effects

ID: 55229156