New insights into fetal mammary gland morphogenesis : differential effects of natural and environmental estrogens

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Speroni , L , Voutilainen , M , Mikkola , M L , Klager , S A , Schaeberle , C M , Sonnenschein , C & Soto , A M 2017 , ' New insights into fetal mammary gland morphogenesis : differential effects of natural and environmental estrogens ' , Scientific Reports , vol. 7 , 40806 . https://doi.org/10.1038/srep40806

Title: New insights into fetal mammary gland morphogenesis : differential effects of natural and environmental estrogens
Author: Speroni, Lucia; Voutilainen, Maria; Mikkola, Marja L.; Klager, Skylar A.; Schaeberle, Cheryl M.; Sonnenschein, Carlos; Soto, Ana M.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2017-01-19
Language: eng
Number of pages: 7
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/176515
Abstract: An increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen's direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E) 14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development. Exposure to 0.1 pM, 10 pM, and 1 nM 17 beta-estradiol (E2) resulted in monotonic inhibition of mammary buds ductal growth. In contrast, Bisphenol-A (BPA) elicited a non-monotonic response. At environmentally relevant doses (1 mu M), BPA significantly increased ductal growth, as previously observed in vivo, while 1 mu M BPA significantly inhibited ductal growth. Ductal branching followed the same pattern. This effect of BPA was blocked by Fulvestrant, a full estrogen antagonist, while the effect of estradiol was not. This method may be used to study the hormonal regulation of mammary gland development, and to test newly synthesized chemicals that are released into the environment without proper assessment of their hormonal action on critical targets like the mammary gland.
Subject: BISPHENOL-A EXPOSURE
IN-UTERO EXPOSURE
BREAST-CANCER
PERINATAL EXPOSURE
ENDOCRINE DISRUPTORS
RELEVANT LEVELS
RAPID ACTION
CD-1 MICE
RISK
HORMONE
1184 Genetics, developmental biology, physiology
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