Prenatal Exposure to Paracetamol Impairs Masculinization

A new study suggests that paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) can inhibit androgens and prostaglandin action during fetal development, resulting in reduced sex drive and impaired male aggressive behavior.

Researchers at the University of Copenhagen (KU, Denmark), the French National Institute of Health and Medical Research (INSERM; Strasbourg, France), and other institutions conducted intrauterine APAP exposure experiments in C57BL/6 mice, who were administered a dosage very close to the recommended dosage for pregnant women. The researchers 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 in neuronal number in the SDN-POA, the brain area associated with reductions in male sexual behavior. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behavior as adults, and had a less aggressive territorial display towards intruders of the same gender. The exposed males also had reduced intromissions and ejaculations during mating. The study was published on May 30, 2017, in Reproduction.

“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 senior author David Møbjerg Kristensen, PhD, of the KU department of biomedical sciences. “Mice exposed to paracetamol at the fetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their fetal development, and this could be seen long afterwards in their adult life. It is very worrying.”

Paracetamol, discovered in 1877, is classified as a mild analgesic, commonly used for the relief of headaches and other minor aches and pains, and is a major ingredient in numerous cold and flu remedies. APAP use during pregnancy has previously been associated with increased risk of childhood asthma and ADHD, but it is unclear whether the relationship is causal.

Related Links:
University of Copenhagen
French National Institute of Health and Medical Research