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

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Harvard

Hay-Schmidt, A, Finkielman, OTE, Jensen, BAH, Høgsbro, CF, Bak Holm, J, Johansen, KH, Jensen, TK, Andrade, AM, Swan, SH, Bornehag, C-G, Brunak, S, Jegou, B, Kristiansen, K & Kristensen, DM 2017, 'Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour', Reproduction (Cambridge, England), bind 154, nr. 2, s. 145-152. https://doi.org/10.1530/REP-17-0165

APA

Hay-Schmidt, A., Finkielman, O. T. E., Jensen, B. A. H., Høgsbro, C. F., Bak Holm, J., Johansen, K. H., Jensen, T. K., Andrade, A. M., Swan, S. H., Bornehag, C-G., Brunak, S., Jegou, B., Kristiansen, K., & Kristensen, D. M. (2017). Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour. Reproduction (Cambridge, England), 154(2), 145-152. https://doi.org/10.1530/REP-17-0165

CBE

Hay-Schmidt A, Finkielman OTE, Jensen BAH, Høgsbro CF, Bak Holm J, Johansen KH, Jensen TK, Andrade AM, Swan SH, Bornehag C-G, Brunak S, Jegou B, Kristiansen K, Kristensen DM. 2017. Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour. Reproduction (Cambridge, England). 154(2):145-152. https://doi.org/10.1530/REP-17-0165

MLA

Vancouver

Author

Hay-Schmidt, Anders ; Finkielman, Olivia T Ejlstrup ; Jensen, Benjamin A H ; Høgsbro, Christine F ; Bak Holm, Jacob ; Johansen, Kristoffer Haurum ; Jensen, Tina Kold ; Andrade, Anderson Martino ; Swan, Shanna H ; Bornehag, Carl-Gustaf ; Brunak, Søren ; Jegou, Bernard ; Kristiansen, Karsten ; Kristensen, David Møbjerg. / Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour. I: Reproduction (Cambridge, England). 2017 ; Bind 154, Nr. 2. s. 145-152.

Bibtex

@article{83557c51ab5342969aa2cd19f5716d13,
title = "Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour",
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 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.",
keywords = "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",
author = "Anders Hay-Schmidt and Finkielman, {Olivia T Ejlstrup} and Jensen, {Benjamin A H} and H{\o}gsbro, {Christine F} and {Bak Holm}, Jacob and Johansen, {Kristoffer Haurum} and Jensen, {Tina Kold} and Andrade, {Anderson Martino} and Swan, {Shanna H} and Carl-Gustaf Bornehag and S{\o}ren Brunak and Bernard Jegou and Karsten Kristiansen and Kristensen, {David M{\o}bjerg}",
note = "{\textcopyright} 2017 Society for Reproduction and Fertility.",
year = "2017",
doi = "10.1530/REP-17-0165",
language = "English",
volume = "154",
pages = "145--152",
journal = "Reproduction",
issn = "1470-1626",
publisher = "BioScientifica Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour

AU - Hay-Schmidt, Anders

AU - Finkielman, Olivia T Ejlstrup

AU - Jensen, Benjamin A H

AU - Høgsbro, Christine F

AU - Bak Holm, Jacob

AU - Johansen, Kristoffer Haurum

AU - Jensen, Tina Kold

AU - Andrade, Anderson Martino

AU - Swan, Shanna H

AU - Bornehag, Carl-Gustaf

AU - Brunak, Søren

AU - Jegou, Bernard

AU - Kristiansen, Karsten

AU - Kristensen, David Møbjerg

N1 - © 2017 Society for Reproduction and Fertility.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acetaminophen/toxicity

KW - Aggression/drug effects

KW - Aniline Compounds/toxicity

KW - Animals

KW - Ejaculation/drug effects

KW - Female

KW - Gestational Age

KW - Male

KW - Mice, Inbred C57BL

KW - Neurons/drug effects

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Preoptic Area/drug effects

KW - Risk Assessment

KW - Sex Characteristics

KW - Sexual Behavior, Animal/drug effects

KW - Territoriality

KW - Urination/drug effects

U2 - 10.1530/REP-17-0165

DO - 10.1530/REP-17-0165

M3 - Journal article

C2 - 28559473

VL - 154

SP - 145

EP - 152

JO - Reproduction

JF - Reproduction

SN - 1470-1626

IS - 2

ER -

ID: 55229156