Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on the BALB/c mouse mammary gland

Russell C. Hovey, Mikiko Asai-Sato, Anni Warri, Barbara Terry-Koroma, Nira Colyn, Erika Ginsburg, Barbara K. Vonderhaar

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31 Scopus citations

Abstract

In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125-50 μg), tamoxifen (TAM, 0.0125-50 μg), and toremifene (TOR, 53 μg) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (12.5 μg) and impaired by exposure to TAM (25 μg). 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 μg 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 μg 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.

Original languageEnglish (US)
Pages (from-to)423-435
Number of pages13
JournalBiology of Reproduction
Volume72
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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Keywords

  • Estradiol
  • Lactation
  • Mammary glands
  • Prolactin
  • Puberty

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Hovey, R. C., Asai-Sato, M., Warri, A., Terry-Koroma, B., Colyn, N., Ginsburg, E., & Vonderhaar, B. K. (2005). Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on the BALB/c mouse mammary gland. Biology of Reproduction, 72(2), 423-435. https://doi.org/10.1095/biolreprod.104.029769