Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring

DES is one of the major disasters in medicine and it is mandatory to tackle and promote programs of DES-related cancer prevention

2017 Study Highlights

  • Diethylstilbestrol (DES) is a synthetic, non-steroidal estrogen of the stilbestrol group acting as an endocrine disruptor.
  • Adverse pregnancy outcomes, infertility, cancer, and early menopause have been identified in women exposed to DES, their offspring, and subsequent generations.

Abstract

Diethylstilbestrol (DES) was an orally active estrogen prescribed to the pregnant women to prevent miscarriages.

DES is known as a ‘biological time bomb’ and long-term effects of DES have been recorded in the mothers exposed to DES and their offspring (DES-daughters and DES-sons). Adverse pregnancy outcomes, infertility, cancer, and early menopause have been discovered in women exposed to DES, and some events occur in their offspring and subsequent generations. An increased risk of breast cancer is not limited to the DES-exposed daughters.

There is an urgent need to find ways to stop the inheritance cycle of DES and prevent adverse effects of DES in the future generations. The present article reviews the health implications of DES exposure and screening exams currently recommended to DES daughters and their offspring.

  • Reproductive toxicology (Elmsford, N.Y.)., Volume 71, August 2017, Pages 71–77, 2017 Apr 28. Image credit jason wilson.
DES DiEthylStilbestrol Resources

Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds

Lessons from diethylstilbestrol : psychosis associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity in the DES-exposed.

2017 Study Abstract

BACKGROUND
In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis.

METHODS
From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip® in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We also compared exposed individuals with (n = 7) and without psychosis (n = 30).

RESULTS
There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9). Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 (ZFP57).

CONCLUSIONS
In utero exposure to DES was not associated with methylation changes at specific CpG or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.

  • Image credit Morgaine. Read and download the full study (free access) on the NCBI, PubMed, PMC5390994, 2017 Apr 13.
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Victimes Suisses du DES : Appel à Témoin

Votre mère a-t-elle pris du Clinestrol, Cyren B, Cyren S, Estril, Estrobene, Oestrostilben ou Syntostrol ?

En 2012, l’émission 36°9, de la chaîne RTS, avait publié un excellent reportage Distilbène: un héritage empoisonné, traitant des conséquences multi-générationnelles du DES – annonçé ici.

Aujourd’hui en 2017, RTS santé recherche des victimes Suisses du DES distilbène – également commercialisé en Suisse de 1953 à 1977 sous les noms de Clinestrol, Cyren B, Cyren S, Estril, Estrobene, Oestrostilben, Syntostrol – une mère à qui on l’aurait prescrit pendant sa grossesse ou des enfants qui en subissent les conséquences.

Veuillez contacter Réseau DES France via leur site sécurisé.

Les journalistes suisses se déplaceront fin mai près de Perpignan, pour interviewer les victimes de la Dépakine et Marine Martin, présidente de l’APESAC.

Les Filles DES de la région Occitanie, prêtes à témoigner de leur parcours, peuvent contacter Réseau DES France, d’ici ce mardi 23, par courriel.

Le Distilbène DES, en savoir plus

Diethylstilbestrol induces oxidative DNA damage

DES exposure results in apoptosis of spermatogonial stem cells in vitro

2017 Study Highlights

  • Exposure of the spermatogonial stem cells to DES produced significant increases in superoxide anion, DNA damage and apoptosis.
  • The male reproductive system can be disrupted by foetal exposure to DES.
  • The flavonoid quercetin reduced intracellular superoxide anions induced by DES.

Abstract

The spermatogonial stem cells (SSCs) are the only germline stem cells in adults that are responsible for the transmission of genetic information from mammals to the next generation. SSCs play a very important role in the maintenance of progression of spermatogenesis and help provide an understanding of the reproductive biology of future gametes and a strategy for diagnosis and treatment of infertility and male reproductive toxicity.

Androgens/oestrogens are very important for the suitable maintenance of male germ cells. There is also evidence confirming the damaging effects of oestrogen-like compounds on male reproductive health.

Diethylstilbestrol induces oxidative DNA damage, resulting in apoptosis of spermatogonial stem cells in vitro, US National Library of Medicine National Institutes of Health, Toxicology, NCBI PubMed PMID: 28315349, 2017 Mar.

Image credit Alessandro.

We investigated the effects in vitro, of diethylstilbestrol (DES) on mouse spermatogonial stem cells separated using Staput unit-gravity velocity sedimentation, evaluating any DNA damage using the Comet assay and apoptotic cells in the TUNEL assay.

Immunocytochemistry assays showed that the purity of isolated mouse spermatogonial cells was 90%, and the viability of these isolated cells was over 96%. Intracellular superoxide anion production (O2) in SSCs was detected using p-Nitro Blue Tetrazolium (NBT) assay. The viability of cells after DES treatment was examined in the CCK8 (cell counting kit-8) cytotoxicity assay.

The study results showed that DES-induced DNA damage causes an increase in intracellular superoxide anions which are reduced by the flavonoid, quercetin. Investigating the molecular mechanisms and biology of SSCs provides a better understanding of spermatogonial stem cell regulation in the testis.

DES DiEthylStilbestrol Resources

Sexual Differentiation of the Brain

Hormones and sexual differentiation of human behavior

Includes Gonadal hormones and sexual differentiation of human behavior : Effects on psychosexual and cognitive development.

by Akira Matsumoto, 1999.

Sexual difference in the brain has long been one of the more intriguing research areas in the field of neuroscience. This thorough and comprehensive text uncovers and explains recent neurobiological and molecular biological studies in the field of neuroscience as they relate to the mechanisms underlying sexual differentiation of the brain.

Attempts have been made to clarify sex differences in the human brain using noninvasive techniques such as magnetic resonance imaging. Sexual Differentiation of the Brain thoroughly examines these techniques and findings, providing an up-to-date, comprehensive overview written by leading researchers in the field.

Chapter 14

Gonadal hormones and sexual differentiation of human behavior: Effects on psychosexual and cognitive development

Melissa Hines is a DES Daughter who has substantial research experience investigating impact of prenatal DES exposure in females and subsequent impact on gender and sexual orientation. She has several books which further investigate these themes of “brain gender”.

Contents
  1. Introduction and Overview
  2. Core Gender Identity
  3. Sexual Orientation
    1. Genetic Females
      1. CAH
      2. DES
    2. Genetic Males
      1. Androgen Insensivity Syndrome (AIS)
      2. Enzymatic Deficiencies
      3. Exposure to DES or Progestins
  4. Gender Role Behaviors
    1. Childhood Play Behavior
    2. Cognitive Abilities
  5. Summary and Conclusions
    References

Testing Medical Treatments : DiEthylStilbestrol

Testing Treatments Interactive, promoting better research for better healthcare

Audio published mid 2016 by Testing Treatments Interactive, promoting better research for better healthcare.

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Man and woman, boy and girl

The differentiation and dimorphism of gender identity from conception to maturity

The differentiation and dimorphism of gender identity from conception to maturity.

Baltimore : Johns Hopkins University Press, 1972 book that combines experimental and clinical data in this report on human development and the relation of sexual differentiation and social roles.

In Man and Woman, Boy and Girl, John Money and Anke Ehrhardt offer a comprehensive account of sexual differentiation using genetics, embryology, endocrinology and neuro-endocrinology, psychology, and anthropology. Their multidisciplinary approach to gender identity avoids the old arguments over nature versus nurture. Money and Ehrhardt focus instead on the interaction of hereditary endowment and environmental influence. Money and Ehrhardt’s work will lead many readers to the conclusion that the differences between man and man, or woman and woman, can be as great as between man and woman.

This was required reading in my human sexuality class in college. I thought it was well presented and researched. It defies some of the gender role and gender identification theories by explaining the gender spectrum in very graphic terms. It will make some people VERY uncomfortable, but it makes a valid point I believe, there are many ways to define gender and how individuals identify with their gender. It does not support the popular theory that we are born genetically predisposed to a particular sexual orientation. Instead the book suggests that regardless of how male or how female you may be genetically you may choose which sex you prefer in your physical or emotional relationships. Blasphemy to some, but it goes a long way to clearing up some of the ambiguity about gender roles and gender identification.

Jonathan Van Voorhees, August 4, 2015.

Problems of Birth Defects

From Hippocrates to Thalidomide and After

From Hippocrates to thalidomide and after : original papers with commentaries by T.V.N. Persaud

A collection of 57 papers and commentaries, arranged in eight sections, discuss the historical aspects, epidemiology, mechanisms, genetics, etiology, prenatal diagnosis, management, and social aspects of birth defects.

  • Paperback: 399 pages
  • Publisher: University Park Press (1977).
  1. Beliefs, Mythology, Magic and Superstition.
    • Congenital malformations in the past.
    • A brief history of teratology to the early 20th century.
  2. Epidemiology of Birth Defects.
    • Classification and nomenclature of morphological defects.
    • Epidemiologic aspects of the problem of congenital malformations.
    • Congenital malformations. A report of a study of series of consecutive births in 24 centres. (Extracts).
    • The incidence of developmental and other genetic abnormalities.
  3. Teratological Mechanisms.
    • Interrelation of the common congenital malformations. Some aetiological implications.
    • Defective regulatory mechanisms in teratogenesis.
    • Mechanisms of teratogenesis.
    • Congenital postural deformities: perinatal associations.
  4. Cytogenetic and Chromosomal Studies.
    • A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis.
    • The detection of chromosomal sex in hermaphrodites from a skin biopsy.
    • The chromosome number of man.
    • Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions.
    • Chromosome abnormality and perinatal death.
    • Cytogenetics of fetal wastage.
    • Spontaneous abortion and aging of human ova and spermatozoa.
    • Where have all the conceptions gone?
    • Genetics of common disorders.
    • Genetic hazards to man from environmental agents.
  5. Environmental Influences and Congenital Abnormalities.
    • Pigs born without eye balls.
    • Congenital cataract following German measles in the mother.
    • The role of viruses in congenital defects.
    • Congenital toxoplasmosis. A prospective study of 378 pregnancies.
    • Therapeutic abortions with a folic acid antagonist, 4-aminopteroyl-glutamic acid (4-amino P.G.A.) administered by the oral route. (Extract).
    • Diskussionsbemerkung von Privatdozent Dr. W. Lenz, Hamburg, zu dem Vortrag von R. A. Pfeiffer und K. Kosenow: Zur Frage der exogenen Entstehung schwerer Extremitatenmissbildungen.
    • Thalidomide and congenital abnormalities.
    • Foetal malformations due to thalidomide.
    • Nonadrenal female pseudohermaphrodism after administration of testosterone to mother during pregnancy.
    • Masculinization of female fetus due to use of orally given progestins.-
    • Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women.
    • Are anti-epileptics harmful in pregnancy? (Extract).
    • Anticonvulsant drugs and congenital abnormalities.
    • Congenital abnormalities and anticonvulsant drugs.
    • A clinical look at the problem of drugs in pregnancy and their effect on the fetus.
    • Intra-uterine methylmercury poisoning in Iraq.
    • Assessing the impact of low level chemicals on development: behavioral and latent effects.
    • A preliminary report of cigarette smoking and the incidence of prematurity. (Extract).
    • Effect of mothers’ smoking habits on birth weight of their children.
    • The fetal alcohol syndrome.
    • Potatoes and spina bifida.
    • The outcome of 625 pregnancies in women subjected to pelvic radium or roentgen irradiation. (Extract).
    • Radiation and pregnancy.
  6. Detection of Environmental Teratogens.
    • Environmental factors in the etiology of human malformations: perspectives and problems of evaluation.
    • Hazards of the first nine months: an epidemiologist’s nightmare.
  7. Prenatal Diagnosis and Management of Congenital Abnormalities.
    • Prenatal diagnosis of genetic disorders. An analysis of experience with 600 cases.
    • Prenatal diagnosis of mongolism by X-ray.
    • Diagnosis of congenital fetal abnormalities by sonography.
    • Amniography for detection of congenital malformations.
    • Diagnosis of human fetal abnormalities by fetography.
    • Genetic counselling-or what can we tell parents?.
    • Pre-, peri- and postnatal prevention of major neuropediatric handicaps.
  8. Social, Ethical, and Medico-Legal Problems.
    • Moral and ethical problems of pre-natal diagnosis.
    • Attitudes toward defective newborns.
    • Ethical and social aspects of treatment of spina bifida.
    • Moral and ethical dilemmas in the special-care nursery.
    • Further References.
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History of the determination of market share for diethylstilbestrol in an era prior to the development of relative denominator values

Gosselin, Raymond A., Thesis Ph. D. University of South Carolina 1995

History of Medicine, 1995.

History of the determination of market share for diethylstilbestrol in an era prior to the development of relative denominator values

Imprint: 1995.
Physical description: 149 pages ; 28 cm.
Thesis: Ph. D. University of South Carolina 1995.
Genre/Technique: Academic dissertations

Topic-MESH

  • Diethylstilbestrol — adverse effects.
  • Drug Industry — history.
  • Pregnancy Complications — drug therapy.
  • Carcinogens.

a book by Raymond A. Gosselin, available at History of Medicine (Shelfmark: IH.U.6.AA9).

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Dissenting Diagnosis

Voices of Conscience from the Medical Profession

dissenting diagnosis book cover image
Dissenting Diagnosis,
Voices of Conscience from the Medical Profession, by Dr Arun Gadre and Dr Abhay Shukla.

Complaints about the state of medical care are increasing in today s India; whether it s unnecessary investigations, botched operations or expensive, sometimes even harmful, medication. But while the unease is widespread, few outside the profession understand the extent to which the medical system is being distorted.

Dr Arun Gadre and Dr Abhay Shukla have gathered evidence from seventy-eight practising doctors, in both the private and public medical sectors, to expose the ways in which vulnerable patients are exploited by a system that promotes unscrupulous medical practices. At a time when the medical sector is growing rapidly, especially in urban areas, with the proliferation of multi-specialty hospitals and the adoption of ever-more sophisticated technologies, rational and ethical medical care is becoming increasingly rare. Honest doctors feel under siege, professional bodies meant to regulate the medical sector fail to do so, and the influence of the powerful pharmaceutical industry becomes even more pervasive.

Drawing on the frank and courageous statements of these seventy-eight doctors dismayed at the state of their profession, Dissenting Diagnosis lays bare the corruption afflicting the medical sector in India and sets out solutions for a healthier future.

  • See more DES books on this Flickr album.
  • Read How Pharmaceutical Companies Entice Doctors Into Prescribing Expensive Medication, the Caravan, 16 April 2016.
  • Read Customer Reviews on Amazon and GoodReads.