A1 Refereed original research article in a scientific journal
Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on the BALB/c mouse mammary gland
Authors: Hovey RC, Asai-Sato M, Warri A, Terry-Koroma B, Colyn N, Ginsburg E, Vonderhaar BK
Publisher: SOC STUDY REPRODUCTION
Publication year: 2005
Journal: Biology of Reproduction
Journal name in source: BIOLOGY OF REPRODUCTION
Journal acronym: BIOL REPROD
Volume: 72
Issue: 2
First page : 423
Last page: 435
Number of pages: 13
ISSN: 0006-3363
DOI: https://doi.org/10.1095/biolreprod.104.029769
Abstract
In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125-50 mug), tamoxifen (TAM, 0.0125-50 mug), and toremifene (TOR, 53 mug) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (112.5 mug) and impaired by exposure to TAM (25 mug). Neonatal treatment with high doses of DES resulted in mammary ducts that displayed extensive dilatation and precocious lactogenesis in postpubertal, nulliparous females. Initiation of this precocious differentiation coincided with the absence of corpora lutea, increased levels of serum prolactin (PRL), and the induction of Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 mug TAM increased alveolar development in postpubertal, nulliparous females similar to that recorded in females treated with low doses of DES. Lower doses of TAM did not affect alveolar development, whereas branching morphogenesis and alveolar development were impaired by higher doses. increased alveolar development in females exposed to 1.25 jig TAM was associated with elevated serum progesterone (P) and increased alveolar development in response to exogenous P. Taken together, our findings demonstrate that neonatal exposure to both DES and TAM exerts long-lasting effects on the proliferation and differentiation of the mammary glands in female BALB/c, primarily as the result of endocrine disruption.
In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125-50 mug), tamoxifen (TAM, 0.0125-50 mug), and toremifene (TOR, 53 mug) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (112.5 mug) and impaired by exposure to TAM (25 mug). Neonatal treatment with high doses of DES resulted in mammary ducts that displayed extensive dilatation and precocious lactogenesis in postpubertal, nulliparous females. Initiation of this precocious differentiation coincided with the absence of corpora lutea, increased levels of serum prolactin (PRL), and the induction of Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 mug TAM increased alveolar development in postpubertal, nulliparous females similar to that recorded in females treated with low doses of DES. Lower doses of TAM did not affect alveolar development, whereas branching morphogenesis and alveolar development were impaired by higher doses. increased alveolar development in females exposed to 1.25 jig TAM was associated with elevated serum progesterone (P) and increased alveolar development in response to exogenous P. Taken together, our findings demonstrate that neonatal exposure to both DES and TAM exerts long-lasting effects on the proliferation and differentiation of the mammary glands in female BALB/c, primarily as the result of endocrine disruption.
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