EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

Marta Axelstad Petersen, Ulla Hass, M. Scholze, Sofie Christiansen, A Kortenkamp, Julie Boberg*

*Corresponding author for this work

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Abstract

Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16-20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.
Original languageEnglish
JournalEndocrine Connections
Volume7
Issue number1
Pages (from-to)139-148
Number of pages10
DOIs
Publication statusPublished - 2018

Keywords

  • acetaminophen
  • anti-androgenic
  • endocrine disrupters
  • estrogenic
  • pesticides
  • phthalates
  • semen quality

Cite this

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title = "EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters",
abstract = "Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16-20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.",
keywords = "acetaminophen, anti-androgenic, endocrine disrupters, estrogenic, pesticides, phthalates, semen quality",
author = "{Axelstad Petersen}, Marta and Ulla Hass and M. Scholze and Sofie Christiansen and A Kortenkamp and Julie Boberg",
year = "2018",
doi = "10.1530/EC-17-0307",
language = "English",
volume = "7",
pages = "139--148",
journal = "Endocrine Connections",
issn = "2049-3614",
publisher = "Bioscientifica",
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}

EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters. / Axelstad Petersen, Marta; Hass, Ulla; Scholze, M.; Christiansen, Sofie; Kortenkamp, A; Boberg, Julie.

In: Endocrine Connections, Vol. 7, No. 1, 2018, p. 139-148.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

AU - Axelstad Petersen, Marta

AU - Hass, Ulla

AU - Scholze, M.

AU - Christiansen, Sofie

AU - Kortenkamp, A

AU - Boberg, Julie

PY - 2018

Y1 - 2018

N2 - Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16-20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

AB - Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16-20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

KW - acetaminophen

KW - anti-androgenic

KW - endocrine disrupters

KW - estrogenic

KW - pesticides

KW - phthalates

KW - semen quality

U2 - 10.1530/EC-17-0307

DO - 10.1530/EC-17-0307

M3 - Journal article

VL - 7

SP - 139

EP - 148

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 1

ER -