Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate

Julie Boberg, Hanna Katarina Lilith Johansson, Niels Hadrup, Karin Dreisig Sørensen, Line Olrik Berthelsen, Kristian Almstrup, Anne Marie Vinggaard, Ulla Hass

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND:
Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk.
METHODS:
We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels.
RESULTS:
Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3.
CONCLUSIONS:
Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. Prostate.
Original languageEnglish
JournalProstate
Volume75
Issue number2
Pages (from-to)126-140
Number of pages15
ISSN0270-4137
DOIs
Publication statusPublished - 2015

Keywords

  • Aging
  • Androgen
  • Anti-androgen
  • Cancer
  • Endocrine disrupters
  • Estrogen
  • mRNA levels
  • Mixture toxicology
  • Prepuberty
  • Prostate
  • Toxicity
  • Toxicology

Cite this

Boberg, Julie ; Johansson, Hanna Katarina Lilith ; Hadrup, Niels ; Sørensen, Karin Dreisig ; Berthelsen, Line Olrik ; Almstrup, Kristian ; Vinggaard, Anne Marie ; Hass, Ulla. / Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate. In: Prostate. 2015 ; Vol. 75, No. 2. pp. 126-140.
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title = "Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate",
abstract = "BACKGROUND:Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk.METHODS:We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels.RESULTS:Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3.CONCLUSIONS:Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. Prostate.",
keywords = "Aging, Androgen, Anti-androgen, Cancer, Endocrine disrupters, Estrogen, mRNA levels, Mixture toxicology, Prepuberty, Prostate, Toxicity, Toxicology",
author = "Julie Boberg and Johansson, {Hanna Katarina Lilith} and Niels Hadrup and S{\o}rensen, {Karin Dreisig} and Berthelsen, {Line Olrik} and Kristian Almstrup and Vinggaard, {Anne Marie} and Ulla Hass",
year = "2015",
doi = "10.1002/pros.22897",
language = "English",
volume = "75",
pages = "126--140",
journal = "Prostate",
issn = "0270-4137",
publisher = "JohnWiley & Sons, Inc.",
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Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate. / Boberg, Julie; Johansson, Hanna Katarina Lilith; Hadrup, Niels; Sørensen, Karin Dreisig; Berthelsen, Line Olrik; Almstrup, Kristian; Vinggaard, Anne Marie; Hass, Ulla.

In: Prostate, Vol. 75, No. 2, 2015, p. 126-140.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate

AU - Boberg, Julie

AU - Johansson, Hanna Katarina Lilith

AU - Hadrup, Niels

AU - Sørensen, Karin Dreisig

AU - Berthelsen, Line Olrik

AU - Almstrup, Kristian

AU - Vinggaard, Anne Marie

AU - Hass, Ulla

PY - 2015

Y1 - 2015

N2 - BACKGROUND:Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk.METHODS:We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels.RESULTS:Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3.CONCLUSIONS:Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. Prostate.

AB - BACKGROUND:Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk.METHODS:We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels.RESULTS:Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3.CONCLUSIONS:Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. Prostate.

KW - Aging

KW - Androgen

KW - Anti-androgen

KW - Cancer

KW - Endocrine disrupters

KW - Estrogen

KW - mRNA levels

KW - Mixture toxicology

KW - Prepuberty

KW - Prostate

KW - Toxicity

KW - Toxicology

U2 - 10.1002/pros.22897

DO - 10.1002/pros.22897

M3 - Journal article

VL - 75

SP - 126

EP - 140

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 2

ER -