Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens.

Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors.

• Publication year

  1995

• Venue

  Environmental Health Perspectives

• Publication date

  1995-10-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1289/EHP.95103S783PMID 8593881PMCID 1518878
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Embryonic estrogen receptors: do they have a physiological function?

  1995cited by this paper
• Mouse lactoferrin gene: a marker for estrogen and epidermal growth factor.

  1995cited by this paper
• Effects of sex hormones on oncogene expression in the vagina and on development of sexual dimorphism of the pelvis and anococcygeus muscle in the mouse.

  1995cited by this paper
• Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites.

  1994cited by this paper
• Aberrant reproductive phenotypes evident in transgenic mice expressing the wild-type mouse estrogen receptor.

  1994cited by this paper
• Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes.

  1994cited by this paper
• Control of Uterine Epithelial Growth and Differentiation: Implications for Estrogen-Associated Neoplasia

  1992cited by this paper
• Immunodetection of estrogen receptors in fetal and neonatal male mouse reproductive tracts.

  1992cited by this paper
• Estrogen receptor expression in the genital tract of female mice treated neonatally with diethylstilbestrol.

  1992cited by this paper
• Immunodetection of estrogen receptors in fetal and neonatal female mouse reproductive tracts.

  1991cited by this paper
• Uterine adenocarcinoma in mice following developmental treatment with estrogens: a model for hormonal carcinogenesis.

  1990cited by this paper
• Female gene expression in the seminal vesicle of mice after prenatal exposure to diethylstilbestrol.

  1989cited by this paper
• Müllerian remnants of male mice exposed prenatally to diethylstilbestrol.

  1987cited by this paper
• Adenocarcinoma, Endometrium, Rat

  1987cited by this paper
• Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol.

  1985cited by this paper
• Vaginal adenosis and adenocarcinoma in mice exposed prenatally or neonatally to diethylstilbestrol.

  1982cited by this paper
• Reduced fertility in female mice exposed transplacentally to diethylstilbestrol (DES).

  1982cited by this paper
• Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol.

  1980cited by this paper
• Diethylstilbestrol-induced upper genital tract abnormalities.

  1979cited by this paper
• Pathological changes in female C3H mice continuously fed diets containing diethylstilbestrol or 17beta--estradiol.

  1978cited by this paper
• Journal Abstracts

  1978cited by this paper
• Follow‐up Study of Male and Female Offspring of DES‐Exposed Mothers

  1977cited by this paper
• Post-stilbestrol secondary syndrome.

  1973cited by this paper

• Functional Changes in the Fallopian Tube: Environmental Factors, Lifestyle, Pathological Conditions and Pharmacological Agents

  2026cites this paper
• Microbes as Resources to Remove PPCPs and Improve Water Quality

  2025cites this paper
• Oral exposure to bisphenol S is associated with alterations in the oviduct proteome of an ovine model, with aggravated effects in overfed females

  2024cites this paper
• In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.

  2023cites this paper
• Imprinting and Reproductive Health: A Toxicological Perspective

  2023cites this paper
• Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

  2023cites this paper
• Obesity III: Obesogen assays: Limitations, strengths, and new directions.

  2022cites this paper
• Evidence of intergenerational transmission of diethylstilbestrol health effects: hindsight and insight

  2021cites this paper
• New frontiers of developmental endocrinology opened by researchers connecting irreversible effects of sex hormones on developing organs.

  2020cites this paper
• Early-life factors, in-utero exposures and endometriosis risk: a meta-analysis.

  2020cites this paper
• Effects of acetaminophen on estrogen-responsive alkaline phosphatase in Ishikawa endometrial cancer cells

  2020cites this paper
• Evidence for germline non-genetic inheritance of human phenotypes and diseases

  2020cites this paper
• Perinatal exposure to bisphenol A at the intersection of stress, anxiety, and depression.

  2020cites this paper
• Prenatal diethylstilbestrol exposure and cancer risk in women

  2019cites this paper
• Systematic Review and Meta-analysis of Testicular Germ Cell Tumors Following In Utero Exposure to Diethylstilbestrol

  2019cites this paper
• Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study.

  2019cites this paper
• Perturbation of Nuclear Hormone Receptors by Endocrine Disrupting Chemicals: Mechanisms and Pathological Consequences of Exposure

  2019cites this paper
• Diethylstilbestrol induces morphological changes in the spermatogonia, Sertoli cells and Leydig cells of adult rat.

  2019cites this paper
• Deltamethrin Alters Thyroid Hormones and Delays Pubertal Development in Male and Female Rats

  2018cites this paper
• 8.22 – Estrogenic Endocrine Disruptors: Molecular Characteristics and Human Impacts☆

  2018cites this paper
• Development of the human female reproductive tract.

  2018cites this paper
• Short-term exposure to bisphenol A affects water and salt intakes differently in male and ovariectomised female rats.

  2018cites this paper
• Timing of Exposure and Bisphenol-A: Implications for Diabetes Development

  2018cites this paper
• Risk for and consequences of endometriosis: A critical epidemiologic review.

  2018cites this paper
• Tissue interactions and estrogenic response during human female fetal reproductive tract development.

  2018cites this paper
• Using Exposomics to Assess Cumulative Risks from Multiple Environmental Stressors

  2018cites this paper
• Sex-Dependent and -Independent Mechanisms in External Genitalia Development

  2017cites this paper
• Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

  2017cites this paper
• Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol.

  2017cites this paper
• Endocrine disruption: Relevance of experimental studies in female animals to human studies

  2017cites this paper
• A 4‐year study of the proportional distribution of male reproductive organ abnormalities in cattle slaughtered at Nyagatare abattoir, Eastern Rwanda

  2017cites this paper
• Epidemiology of Uterine Fibroids: From Menarche to Menopause.

  2016cites this paper
• Chromosomal and Endocrinological Origins of Sex

  2016cites this paper
• Effects of Prenatal Environmental Exposures on the Development of Endometriosis in Female Offspring

  2016cites this paper
• TRIENNIAL REPRODUCTION SYMPOSIUM: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A.

  2016cites this paper
• TRIENNIAL REPRODUCTION SYMPOSIUM: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A.

  2016cites this paper
• Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs)

  2015cites this paper
• Endocrine-Disrupting Compounds: Measurement in Tampa Bay, Removal from Sewage and Development of an Estrogen Receptor Model

  2015cites this paper
• Neonatal Menstruation Explains Epidemiological Links between Fetomaternal Conditions and Adolescent Endometriosis

  2015cites this paper
• In utero exposure to the oestrogen mimic diethylstilbestrol disrupts gonadal development in a viviparous reptile.

  2015influential citation
• A multi-generational study on low-dose BPA exposure in Wistar rats: effects on maternal behavior, flavor intake and development.

  2014cites this paper
• Mechanisms of estrogenic endocrine disruption of female puberty and reproduction and functions of LHFPL2 on distal reproductive tract development

  2014influential citation
• Rapid actions of xenoestrogens disrupt normal estrogenic signaling.

  2014cites this paper
• Endocrine-disrupting chemicals: elucidating our understanding of their role in sex and gender-relevant end points.

  2014cites this paper
• Prenatal diethylstilbestrol exposure and risk of uterine leiomyomata in the Nurses' Health Study II.

  2014cites this paper
• Prevention of Endometriosis

  2014cites this paper
• In utero exposure and endometriosis

  2014cites this paper
• Routes and mechanisms of embryonic hormone exposure and endocrine disruption in a viviparous lizard

  2013cites this paper
• Endocrine disruptors and falling sperm counts: lessons learned or not!

  2013cites this paper
• Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny.

  2013cites this paper
• Exposure to diethylstilbestrol during sensitive life stages: a legacy of heritable health effects.

  2013influential citation
• Environmental pollutants and diseases of sexual development in humans and wildlife in South Africa: harbingers of impact on overall health?

  2012cites this paper
• State of the Science of Endocrine Disrupting Chemicals - 2012

  2012cites this paper
• Developmental Exposure to Endocrine Disruptors and Ovarian Function

  2012cites this paper
• Epigenetic control of endocrine disrupting chemicals on gynecological disease: Focused on phthalates

  2012influential citation
• Endocrine Disruptors: Passage and Actions in Human Placenta

  2012cites this paper
• [Endocrine disruptors: echoes of congress of Endocrinology in 2012].

  2012cites this paper
• Fetal and Neonatal Endocrine Disruptors

  2012cites this paper
• Perinatal Exposure to Endocrine Disrupting Chemicals with Estrogenic Activity and the Development of Obesity

  2011cites this paper
• Neonatal diethylstilbestrol exposure disrupts female reproductive tract structure/function via both direct and indirect mechanisms in the hamster.

  2011cites this paper
• Prenatal exposure to diethylstilbestrol and long-term impact on the breast and reproductive tract in humans and mice

  2011cites this paper
• Perspectives on endocrine disruptor effects on metabolic sensors.

  2011cites this paper
• Endocrine-disrupting Chemicals (EDCs) in Mammals

  2011cites this paper
• New Directions in the Epidemiology of Uterine Fibroids

  2010cites this paper
• Cancer risk in DES daughters

  2010cites this paper
• The Impact of Endocrine Disruptors on Endocrine Targets

  2010cites this paper
• [Environmental contaminants and endocrine disruptors].

  2010influential citation
• A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats.

  2010cites this paper
• Pesticide use and self-reported uterine leiomyomata among farm women: an analysis of the Agricultural Health Study with assessment of outcome misclassification

  2010cites this paper
• Endocrine Disruption and Breast Cancer Risk

  2010cites this paper
• Janneke VerloopFlora E. van Leeuwen • Theo J. M. HelmerhorstHester H. van Boven •

  2010cites this paper
• A structural view of nuclear hormone receptor: endocrine disruptor interactions

  2010cites this paper
• Neonatal Exposure to Estrogen and Estrogen Receptor Agonists and Antagonists: Effects on the Adult Endometrial Proteome and Morphoregulatory Gene Expression in the Neonatal Uterus

  2010cites this paper
• Impact of environmental endocrine disrupting chemicals on the development of obesity

  2010cites this paper
• Response of adult mouse uterus to early disruption of estrogen receptor-alpha signaling is influenced by Krüppel-like factor 9.

  2010cites this paper
• Estrogenic Endocrine Disruptors: Molecular Characteristics and Human Impacts

  2010cites this paper
• The impact of endocrine disruptors on endocrine targets.

  2010cites this paper
• Transplacental transfer and biotransformation of genistein in human placenta.

  2010cites this paper
• Environmental Endocrine Disruptors and Male Reproductive Toxicology

  2010cites this paper
• Endocrine-disrupting chemicals: an Endocrine Society scientific statement.

  2009cites this paper
• Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies.

  2009cites this paper
• Cytogenetic evaluation for genotoxicity of bisphenol-A in bone marrow cells of Swiss albino mice.

  2009cites this paper
• Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague-Dawley rats.

  2009cites this paper
• Risk Assessment of Soybean-Based Phytoestrogens

  2009cites this paper
• Environmental estrogens and obesity.

  2009cites this paper
• Reproductive toxicity in Xenopus tropicalis after developmental exposure to environmental concentrations of ethynylestradiol.

  2009cites this paper
• Endocrinal toxicity of industrial solvents--a mini review.

  2009cites this paper
• Development of a Bio-Assay for Estrogens using Estrogen Receptor Alpha Gene Expression by MCF7 Cells as Biomarker

  2009cites this paper
• Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus.

  2009cites this paper
• Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A

  2008cites this paper
• The development and implementation of biomarker assays for estrogenic endocrine disruptors

  2008cites this paper
• Effects of endocrine disruptors on obesity.

  2008influential citation
• Paracrine mediators of endometrial growth and differentiation

  2008cites this paper
• A new 'crowded uterine horn' mouse model for examining the relationship between foetal growth and adult obesity.

  2008cites this paper
• A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells.

  2008cites this paper
• No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice.

  2008cites this paper
• DEVELOPMENTAL EXPOSURE TO ENDOCRINE DISRUPTERS : NEUROBEHAVIORAL EFFECTS IN AN ANIMAL MODEL

  2008cites this paper
• Developmental exposure to endocrine disruptors and the obesity epidemic.

  2007cites this paper
• Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

  2007cites this paper
• Analysis of gene expression profiles in the offspring of rats following maternal exposure to xenoestrogens.

  2007cites this paper