Prenatal exposure to low doses of bisphenol a increases pituitary proliferation and gonadotroph number in female mice offspring at birth

Katherine E. Brannick, Zelieann R Craig, Ashley D. Himes, Jackye R. Peretz, Wei Wang, Jodi A. Flaws, Lori T. Raetzman

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading to widespread human exposure. Although prenatal exposure to BPA can impact reproductive function in the adult, the effects of BPA on the developing pituitary are unknown. We hypothesized that prenatal exposure to low doses of BPA impacts gonadotroph cell number or parameters of hormone synthesis. To test this, pregnant mice were administered 0.5 μg/kg/day of BPA, 50 μg/ kg/day of BPA, or vehicle beginning on Embryonic Day 10.5. At parturition, pituitaries from female offspring exposed in utero to either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels and immunohistochemistry. Coincidently, gonadotroph number also increased in treated females. However, we observed a dichotomy between mRNA levels of Lhb and Fshb. Female mice exposed to 0.5 μg/kg/day BPA had increased mRNA levels of gonadotropins and the gonadotropinreceptor hormone (GNRH) receptor (Gnrhr), which mediates GNRH regulation of gonadotropin production and release. In contrast, mice treated with 50 μg/kg/day of BPA had decreased gonadotropin mRNA levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph differentiation. No other pituitary hormones were altered on the day of birth in response to in utero BPA exposure, and male pituitaries showed no change in the parameters tested. Collectively, these results show that prenatal exposure to BPA affects pituitary gonadotroph development in females.

Original languageEnglish (US)
Article numberArticle 82
JournalBiology of Reproduction
Volume87
Issue number4
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

Fingerprint

Gonadotrophs
Parturition
Gonadotropins
Hormones
Messenger RNA
bisphenol A
Food Packaging
Endocrine Disruptors
Food and Beverages
Plasticizers
Pituitary Hormones
Pituitary Gland
Reproduction

Keywords

  • Anterior pituitary
  • Bisphenol A (BPA)
  • Development
  • Developmental biology
  • Endocrine disruptors
  • Environmental contaminants and toxicants
  • Follicle-stimulating hormone (FSH)
  • Gonadotrophs
  • Gonadotropins
  • Luteinizing hormone (LH)
  • Pituitary

ASJC Scopus subject areas

  • Cell Biology

Cite this

Prenatal exposure to low doses of bisphenol a increases pituitary proliferation and gonadotroph number in female mice offspring at birth. / Brannick, Katherine E.; Craig, Zelieann R; Himes, Ashley D.; Peretz, Jackye R.; Wang, Wei; Flaws, Jodi A.; Raetzman, Lori T.

In: Biology of Reproduction, Vol. 87, No. 4, Article 82, 01.10.2012.

Research output: Contribution to journalArticle

Brannick, Katherine E. ; Craig, Zelieann R ; Himes, Ashley D. ; Peretz, Jackye R. ; Wang, Wei ; Flaws, Jodi A. ; Raetzman, Lori T. / Prenatal exposure to low doses of bisphenol a increases pituitary proliferation and gonadotroph number in female mice offspring at birth. In: Biology of Reproduction. 2012 ; Vol. 87, No. 4.
@article{9702f49a304c4338acefb9097902da82,
title = "Prenatal exposure to low doses of bisphenol a increases pituitary proliferation and gonadotroph number in female mice offspring at birth",
abstract = "The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading to widespread human exposure. Although prenatal exposure to BPA can impact reproductive function in the adult, the effects of BPA on the developing pituitary are unknown. We hypothesized that prenatal exposure to low doses of BPA impacts gonadotroph cell number or parameters of hormone synthesis. To test this, pregnant mice were administered 0.5 μg/kg/day of BPA, 50 μg/ kg/day of BPA, or vehicle beginning on Embryonic Day 10.5. At parturition, pituitaries from female offspring exposed in utero to either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels and immunohistochemistry. Coincidently, gonadotroph number also increased in treated females. However, we observed a dichotomy between mRNA levels of Lhb and Fshb. Female mice exposed to 0.5 μg/kg/day BPA had increased mRNA levels of gonadotropins and the gonadotropinreceptor hormone (GNRH) receptor (Gnrhr), which mediates GNRH regulation of gonadotropin production and release. In contrast, mice treated with 50 μg/kg/day of BPA had decreased gonadotropin mRNA levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph differentiation. No other pituitary hormones were altered on the day of birth in response to in utero BPA exposure, and male pituitaries showed no change in the parameters tested. Collectively, these results show that prenatal exposure to BPA affects pituitary gonadotroph development in females.",
keywords = "Anterior pituitary, Bisphenol A (BPA), Development, Developmental biology, Endocrine disruptors, Environmental contaminants and toxicants, Follicle-stimulating hormone (FSH), Gonadotrophs, Gonadotropins, Luteinizing hormone (LH), Pituitary",
author = "Brannick, {Katherine E.} and Craig, {Zelieann R} and Himes, {Ashley D.} and Peretz, {Jackye R.} and Wei Wang and Flaws, {Jodi A.} and Raetzman, {Lori T.}",
year = "2012",
month = "10",
day = "1",
doi = "10.1095/biolreprod.112.100636",
language = "English (US)",
volume = "87",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "4",

}

TY - JOUR

T1 - Prenatal exposure to low doses of bisphenol a increases pituitary proliferation and gonadotroph number in female mice offspring at birth

AU - Brannick, Katherine E.

AU - Craig, Zelieann R

AU - Himes, Ashley D.

AU - Peretz, Jackye R.

AU - Wang, Wei

AU - Flaws, Jodi A.

AU - Raetzman, Lori T.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading to widespread human exposure. Although prenatal exposure to BPA can impact reproductive function in the adult, the effects of BPA on the developing pituitary are unknown. We hypothesized that prenatal exposure to low doses of BPA impacts gonadotroph cell number or parameters of hormone synthesis. To test this, pregnant mice were administered 0.5 μg/kg/day of BPA, 50 μg/ kg/day of BPA, or vehicle beginning on Embryonic Day 10.5. At parturition, pituitaries from female offspring exposed in utero to either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels and immunohistochemistry. Coincidently, gonadotroph number also increased in treated females. However, we observed a dichotomy between mRNA levels of Lhb and Fshb. Female mice exposed to 0.5 μg/kg/day BPA had increased mRNA levels of gonadotropins and the gonadotropinreceptor hormone (GNRH) receptor (Gnrhr), which mediates GNRH regulation of gonadotropin production and release. In contrast, mice treated with 50 μg/kg/day of BPA had decreased gonadotropin mRNA levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph differentiation. No other pituitary hormones were altered on the day of birth in response to in utero BPA exposure, and male pituitaries showed no change in the parameters tested. Collectively, these results show that prenatal exposure to BPA affects pituitary gonadotroph development in females.

AB - The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading to widespread human exposure. Although prenatal exposure to BPA can impact reproductive function in the adult, the effects of BPA on the developing pituitary are unknown. We hypothesized that prenatal exposure to low doses of BPA impacts gonadotroph cell number or parameters of hormone synthesis. To test this, pregnant mice were administered 0.5 μg/kg/day of BPA, 50 μg/ kg/day of BPA, or vehicle beginning on Embryonic Day 10.5. At parturition, pituitaries from female offspring exposed in utero to either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels and immunohistochemistry. Coincidently, gonadotroph number also increased in treated females. However, we observed a dichotomy between mRNA levels of Lhb and Fshb. Female mice exposed to 0.5 μg/kg/day BPA had increased mRNA levels of gonadotropins and the gonadotropinreceptor hormone (GNRH) receptor (Gnrhr), which mediates GNRH regulation of gonadotropin production and release. In contrast, mice treated with 50 μg/kg/day of BPA had decreased gonadotropin mRNA levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph differentiation. No other pituitary hormones were altered on the day of birth in response to in utero BPA exposure, and male pituitaries showed no change in the parameters tested. Collectively, these results show that prenatal exposure to BPA affects pituitary gonadotroph development in females.

KW - Anterior pituitary

KW - Bisphenol A (BPA)

KW - Development

KW - Developmental biology

KW - Endocrine disruptors

KW - Environmental contaminants and toxicants

KW - Follicle-stimulating hormone (FSH)

KW - Gonadotrophs

KW - Gonadotropins

KW - Luteinizing hormone (LH)

KW - Pituitary

UR - http://www.scopus.com/inward/record.url?scp=84869395197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869395197&partnerID=8YFLogxK

U2 - 10.1095/biolreprod.112.100636

DO - 10.1095/biolreprod.112.100636

M3 - Article

C2 - 22875908

AN - SCOPUS:84869395197

VL - 87

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 4

M1 - Article 82

ER -