Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations.

Full Abstract

The synthetic estrogen diethylstilbestrol (DES) is a potent perinatal endocrine disruptor. In humans and experimental animals, exposure to DES during critical periods of reproductive tract differentiation permanently alters estrogen target tissues and results in long-term abnormalities such as uterine neoplasia that are not manifested until later in life. Using the developmentally exposed DES mouse, multiple mechanisms have been identified that play a role in its carcinogenic and toxic effects. Analysis of the DES murine uterus reveals altered gene expression pathways that include an estrogen-regulated component. Thus, perinatal DES exposure, especially at low doses, offers the opportunity to study effects caused by weaker environmental estrogens and provides an example of the emerging scientific field termed the developmental origin of adult disease. As a model endocrine disruptor, it is of particular interest that even low doses of DES increase uterine tumor incidence. Additional studies have verified that DES is not unique; when other environmental estrogens are tested at equal estrogenic doses, developmental exposure results in increased incidence of uterine neoplasia similar to that caused by DES. Interestingly, our data suggest that this increased susceptibility for tumors is passed on from the maternal lineage to subsequent generations of male and female descendants; the mechanisms involved in these transgenerational events include genetic and epigenetic events. Together, our data point out the unique sensitivity of the developing organism to endocrine-disrupting chemicals, the occurrence of long-term effects after developmental exposure, and the possibility for adverse effects to be transmitted to subsequent generations.

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Author information

Author/s: Newbold, Retha R (RR); Padilla-Banks, Elizabeth (E); Jefferson, Wendy N (WN);

Affiliation: Developmental Endocrinology and Endocrine Disruptor Section, Mail-Drop E4-02, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. newbold1(-atsign-)niehs.nih.gov

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural; Review

Journal: Endocrinology (Endocrinology), published in United States. (Language: eng)

Reference: 2006-Jun; vol 147 (issue 6 Suppl) : pp S11-7

Dates: Created 2006/05/18; Completed 2006/06/22; Revised 2006/11/15;

PMID: 16690809, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Diethylstilbestrol - toxicity
Endocrine Disruptors - toxicity
Environmental Exposure
Epigenesis, Genetic - drug effects
Estrogens - toxicity
Female
Gene Expression - drug effects

Genital Neoplasms, Female - chemically induced; genetics
Genital Neoplasms, Male - chemically induced; genetics
Humans
Infant, Newborn
Male
Pregnancy
Prenatal Exposure Delayed Effects
Uterine Neoplasms - chemically induced

Associated Chemicals: Endocrine Disruptors (0) ; Estrogens (0) ; Diethylstilbestrol (56-53-1)

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