skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

Abstract

Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor {alpha} (ER{alpha}) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ER{alpha},more » EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA{sub B} receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGF{alpha}. Collectively, these results suggest that the disrupted sexual differentiation of the POA by prenatal EDC exposures is already evident as early as the day after birth, effects that may change the trajectory of postnatal development and compromise adult reproductive function.« less

Authors:
;  [1];  [1];  [2];  [2]
  1. Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
21535268
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 252; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2011.01.012; PII: S0041-008X(11)00022-6; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADULTS; APOPTOSIS; ESTRADIOL; FEMALES; GENES; HYPOTHALAMUS; MALES; NUCLEI; POLYCHLORINATED BIPHENYLS; POLYMERASE CHAIN REACTION; RATS; RECEPTORS; SEX; AGE GROUPS; ANIMALS; AROMATICS; BODY; BRAIN; CENTRAL NERVOUS SYSTEM; CHLORINATED AROMATIC HYDROCARBONS; ESTRANES; ESTROGENS; GENE AMPLIFICATION; HALOGENATED AROMATIC HYDROCARBONS; HORMONES; HYDROXY COMPOUNDS; MAMMALS; MEMBRANE PROTEINS; NERVOUS SYSTEM; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANS; PROTEINS; RODENTS; STEROID HORMONES; STEROIDS; VERTEBRATES

Citation Formats

Dickerson, Sarah M., Cunningham, Stephanie L., Gore, Andrea C., E-mail: andrea.gore@mail.utexas.edu, Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.01.012.
Dickerson, Sarah M., Cunningham, Stephanie L., Gore, Andrea C., E-mail: andrea.gore@mail.utexas.edu, Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, & Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus. United States. doi:10.1016/j.taap.2011.01.012.
Dickerson, Sarah M., Cunningham, Stephanie L., Gore, Andrea C., E-mail: andrea.gore@mail.utexas.edu, Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712. Fri . "Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus". United States. doi:10.1016/j.taap.2011.01.012.
@article{osti_21535268,
title = {Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus},
author = {Dickerson, Sarah M. and Cunningham, Stephanie L. and Gore, Andrea C., E-mail: andrea.gore@mail.utexas.edu and Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712 and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712},
abstractNote = {Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor {alpha} (ER{alpha}) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ER{alpha}, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA{sub B} receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGF{alpha}. Collectively, these results suggest that the disrupted sexual differentiation of the POA by prenatal EDC exposures is already evident as early as the day after birth, effects that may change the trajectory of postnatal development and compromise adult reproductive function.},
doi = {10.1016/j.taap.2011.01.012},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 252,
place = {United States},
year = {2011},
month = {4}
}