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Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

BACKGROUND: Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. OBJE...

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Detalles Bibliográficos
Autores principales: Fernández, Marina, Bianchi, Maria, Lux-Lantos, Victoria, Libertun, Carlos
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685838/
https://www.ncbi.nlm.nih.gov/pubmed/19479018
http://dx.doi.org/10.1289/ehp.0800267
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author Fernández, Marina
Bianchi, Maria
Lux-Lantos, Victoria
Libertun, Carlos
author_facet Fernández, Marina
Bianchi, Maria
Lux-Lantos, Victoria
Libertun, Carlos
author_sort Fernández, Marina
collection PubMed
description BACKGROUND: Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. OBJECTIVES: We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats. METHODS: Female rats were injected subcutaneusly, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 μg/50 μL (high) or 50 μg/50 μL (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP(3)), and extracellular signal-regulated kinase(1/2) (ERK(1/2)). RESULTS: Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP(3) formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK(1/2) activation. CONCLUSIONS: Neonatal exposure to BPA altered reproductive parameters and hypothalamic–pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling.
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spelling pubmed-26858382009-05-27 Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats Fernández, Marina Bianchi, Maria Lux-Lantos, Victoria Libertun, Carlos Environ Health Perspect Research BACKGROUND: Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. OBJECTIVES: We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats. METHODS: Female rats were injected subcutaneusly, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 μg/50 μL (high) or 50 μg/50 μL (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP(3)), and extracellular signal-regulated kinase(1/2) (ERK(1/2)). RESULTS: Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP(3) formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK(1/2) activation. CONCLUSIONS: Neonatal exposure to BPA altered reproductive parameters and hypothalamic–pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling. National Institute of Environmental Health Sciences 2009-05 2009-01-07 /pmc/articles/PMC2685838/ /pubmed/19479018 http://dx.doi.org/10.1289/ehp.0800267 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Fernández, Marina
Bianchi, Maria
Lux-Lantos, Victoria
Libertun, Carlos
Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title_full Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title_fullStr Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title_full_unstemmed Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title_short Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
title_sort neonatal exposure to bisphenol a alters reproductive parameters and gonadotropin releasing hormone signaling in female rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685838/
https://www.ncbi.nlm.nih.gov/pubmed/19479018
http://dx.doi.org/10.1289/ehp.0800267
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