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Acetaminophen in pregnancy reduces masculinity?

Acetaminophen taken during pregnancy can inhibit, in mice, both male sex drive and aggressive behavior according to new research from the University of Copenhagen.


Acetominophen (Paracetamol in the UK) is popular for relieving pain. But if you are pregnant, you should think twice before popping a few pills. According to new research using mice as the model animals, Paracetamol actually damages developing male neurons leading to behavior changes.

Previous studies on mice have shown that paracetamol can inhibit development of the male sex hormone testosterone in male fetuses, thus increasing the risk for malformation of the testicles in pups. But, a reduced level of testosterone at the fetal stage also significantly affects the behavior of adult males, says David Møbjerg Kristensen PhD, a researcher in the Department of Biomedical Sciences and at the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences.

The findings are published in the journal Reproduction.
"We had already demonstrated that a reduced level of testosterone means male physical characteristics do not develop as they should — which affects sex drive. In our new trial, mice exposed to paracetamol in their fetal stages were simply unable to copulate the same as control animals. Male [brain] programming had not properly established during development and this could be seen long afterwards in their adult life. It is very worrying."

David Møbjerg Kristensen PhD, Institut national de la santé et de la recherche médicale (Inserm), and The International Research Symposium on Engineering and Technology (IRSET), Rennes, France, and Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark

The dosage administered to the mice was very close to the recommended dosage women are told they can take while pregnant. Because the trials are restricted to mice, the results cannot be transferred directly to humans. But, researchers' are very certain about the harmful effects of paracetamol. It would be unethical to undertake a similar trial on humans, explains Møbjerg Kristensen.

Testosterone is the primary male sex hormone that not only helps develop the male body, but also male programming of the brain. Masculine behaviors observed by researchers involved aggressiveness to other male mice, their ability to copulate, and their need for territorial marking. The mice affected by paracetamol reacted significantly more passively than normal in all three parameters. (1) They did not attack other males, (2) they were unable to copulate and (3) they behaved more like female mice when marking territory with urine.

After observing these changed behavioral patterns, Prof. Anders Hay-Schmidt, at the Department of Neuroscience and Pharmacology, University of Copenhagen, investigated specific effects of a lack of testosterone on the brain. The results showed up clearly there as well.
"The area of the brain that controls sex drive — the sexual dimorphic nucleus — had half the neurons in the mice that had received paracetamol as in the control mice. The inhibition of testosterone also led to halving of the activity in an area of the brain significant for male characteristics."

This study focused on the effect of paracetamol on masculine characteristics but paracetamol in pregnancy also has the potential to influence the subsequent lives of female mice. In 2016, researchers published a study showing that female mice had fewer eggs in their ovaries if their mothers had been given paracetamol during pregnancy. This led to femlae mice becoming infertile more quickly.

But even if paracetamol is harmful, that does not mean it should never be taken when pregnant.

"I personally think people should think carefully before taking medicine. These days it has become so common to take paracetamol we forget it is medicine — and all medicine has side effects. If you are ill, you should naturally take the medicine you need. After all, having a sick mother is the most harmful for the fetus," says Møbjerg Kristensen, and that pregnant women should continue to follow the guidelines given by their country's health authorities and to contact their general practioner if in doubt about their use of paracetamol.

Abstract
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 fetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behavior 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 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. 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 behavior 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.

Other authors: 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.


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Jun 30, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




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