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.
Lessons from diethylstilbestrol : psychosis associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity in the DES-exposed.
2017 Study Abstract
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.
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).
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).
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.
Aujourd’hui en 2017, RTS santérecherche des victimes Suissesdu DESdistilbène – 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.
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.
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.
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.
Hormones and sexual differentiation of human behavior
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.
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”.
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.
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).
Beliefs, Mythology, Magic and Superstition.
Congenital malformations in the past.
A brief history of teratology to the early 20th century.
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.
Interrelation of the common congenital malformations. Some aetiological implications.