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Title: Environmental signaling: from environmental estrogens to endocrine‐disrupting chemicals and beyond
Summary

The landmark report (Herbstet al. 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed thatDESwas the carcinogen and exposure toDEScaused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero.DESwas also being used in agriculture and we discovered, at the first meeting onEstrogens in the Environmentin 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated howDESand other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At theWingspread Conference on the Human‐Wildlife Connectionin 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals alter cell differentiation. Since 2010, research has shown that trauma and other behavioral inputs can function as ‘environmental signals,’ can be encoded in gene regulation networks in a variety of cells and organs, and can be passed on to subsequent generations. So now we come full circle: environmental chemicals mimic hormones or other metabolic signaling molecules and now behavioral experience can be transduced into chemical signals that also modify gene expression.

 
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NSF-PAR ID:
10245497
Author(s) / Creator(s):
 
Publisher / Repository:
Wiley-Blackwell
Date Published:
Journal Name:
Andrology
Volume:
4
Issue:
4
ISSN:
2047-2919
Page Range / eLocation ID:
p. 684-694
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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