Prenatal Acetaminophen Linked To Decreased Masculinization and Testosterone in Male Offspring

MedicalResearch.com Interview with:
David M. Kristensen, PhD
Assistant Professor                                                                                                         Novo Nordisk Foundation Center for Protein Research
Faculty of Health and Medical Sciences, University of Copenhagen,
Blegdamsvej 3A, DK-2200 Copenhagen, Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have demonstrated that a reduced level of testosterone during fetal life by paracetamol means that male characteristics do not develop as they should. This also affects sex drive. In the trial, mice exposed to paracetamol at the foetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their foetal development and this could be seen long afterwards in their adult life. Moreover, 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. The inhibition of testosterone seem to have led to less activity in an area of the brain that is significant for male characteristics.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Giving medical advice is not my job. And I would like to emphasize that pregnant women should continue to follow the guidelines given by their country’s health authorities and recommend people to contact their GP if in doubt about the use of paracetamol. If you are ill, you should naturally take the medicine and follow your medical doctors advice. After all, having a sick mother much data show is more harmful for the foetus. However, my colleagues and I have seen so much data from several studies now on the effect paracetamol that we are getting very worried. Moreover, our own data from previous studies show that many pregnant women take paracetamol and forget it is a medicine. And all medicine has side effects.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Testosterone is the primary male sex hormone that helps develop the male body and male programming of the brain. The masculine behaviours changes in mice observed involved aggressiveness to other male mice, ability to copulate and the need for territorial marking. As mentioned, the mice reacted significantly more passively than normal for all three parameters. They did not attack other males, they were unable to copulate and behaved more like female mice when it come to urinary territorial marking. Taken these data into consideration, I think it could be interesting to do more rodents experiments to understand more of the mechanism of this fetal programming and see if children included in cohort that have been exposed during fetal life to paracetamol have changes in e.g. behaviour.

MedicalResearch.com: Is there anything else you would like to add?

Response: In 2016, we published a study showing that female mice had fewer eggs in their ovaries if their mothers had had paracetamol during pregnancy and this resulted in premature infertility. So this show that it is probably not only males that get affected by fetal paractamol exposure.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Reproduction. 2017 Aug;154(2):145-152. doi: 10.1530/REP-17-0165. Epub 2017 May 30.

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

Hay-Schmidt A1, Finkielman OTE1, Jensen BAH2, Høgsbro CF2, Bak Holm J2, Johansen KH2, Jensen TK3, Andrade AM4, Swan SH5, Bornehag CG5,6, Brunak S7, Jegou B8,9, Kristiansen K2, Kristensen DM10,7.

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Last Updated on June 23, 2017 by Marie Benz MD FAAD