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

Le Distilbène en 2016 (4/4)

Que retenir du guide pratique DES destinés aux professionnels de santé?

Vidéo publiée le 1er septembre 2016 par l’ Association Réseau DES FRANCE DISTILBENE.

Synthèse de l’étude Distilbène 3 générations, 2016.

Guide Pratique

Suite à l’étude Distilbène 3 générations qu’elle a initiée en 2013, l’association Réseau D.E.S. France a publié, fin 2015, un guide pratique pour les professionnels de la santé, synthétisant les données actuelles de la science. Deux versions sont à télécharger:

Le Distilbène DES, en savoir plus

Le Distilbène en 2016 (3/4)

Conséquences pour les petits-enfants DES

Vidéo publiée le 1er septembre 2016 par l’ Association Réseau DES FRANCE DISTILBENE.

En 2016, quelles sont les conséquences du DES pour la troisième génération?

Guide Pratique

Suite à l’étude Distilbène 3 générations qu’elle a initiée en 2013, l’association Réseau D.E.S. France a publié, fin 2015, un guide pratique pour les professionnels de la santé, synthétisant les données actuelles de la science. Deux versions sont à télécharger:

Le Distilbène DES, en savoir plus

Le Distilbène en 2016 (2/4)

Conséquences pour les mères, les filles et les fils DES

Vidéo publiée le 1er septembre 2016 par l’ Association Réseau DES FRANCE DISTILBENE.

En 2016, quelles sont les conséquences du DES pour les mères, filles et fils exposés?

Guide Pratique

Suite à l’étude Distilbène 3 générations qu’elle a initiée en 2013, l’association Réseau D.E.S. France a publié, fin 2015, un guide pratique pour les professionnels de la santé, synthétisant les données actuelles de la science. Deux versions sont à télécharger:

Le Distilbène DES, en savoir plus

DiEthylStilbestrol Gender Identity Controversy

“a very good possibility that DES is was caused me to be trans…”

Video published on 11 June 2016 by DES Daugther Network channel via Dion Lim 5/6/11pm weeknight anchor/reporter at WTSP/CBS .

It was a pill meant to prevent miscarriages…

Can a drug manipulate gender identity, cause people to be trans, asks Dion Lim?
Well, I know many DES sons who can confirm that yes, it did happen.

More DES DiEthylStilbestrol Resources

Prenatal female hormone administration and psychosexual development in human males

Human personality is associated with prenatal hormone exposure

Abstract

ScienceDirect Psychoneuroendocrinology, doi:10.1016/0306-4530(80)90032-3, Volume 5, Issue 4, 1980, Pages 269–285 and Popline Document Number: 001953, node/460051, 1980 Dec.

Male personality by Meghana Kulkarni.

  • Considerable data exist from animal research relating prenatal hormone levels to postnatal behaviors in the male. The data from human males are few. One strategy for testing this association is the study of humans exposed prenatally to exogenous ‘pregnancy maintaining hormones’.
  • A follow-up study was conducted on 62 adult males prenatally exposed to exogenous sex hormones. Fifty-eight young adult males exposed to one of four hormone regimens were matched against nonhormone exposed controls. There were 17 males exposed to diethylstilbestrol (DES), 22 exposed to DES and natural progesterone, 10 to natural progesterone only, and 13 to synthetic progesterone.
  • Subjects were interviewed – to ascertain their psychosexual development during boyhood and adolescence and sexual functioning during adolescence and adulthood – and administered the Bem Sex-Role Inventory (BSRI), the Guilford-Zimmerman Temperament Survey (GZTS), the Strong Vocational Interest Blank (SVIB), and the Embedded Figures Test (EFT).
  • The specific drug, total dosage, and time of drug administration i.e., the trimester of exposure, were significantly associated with several aspects of boyhood, adolescent, and adult psychosexual development on interview and with differences in scales of the psychometric tests.
  • The behavior of subjects exposed to each substance was compared to the control behavior and to behavior of those exposed to other substances. The femininity scale was elevated for 3 of the 4 drug regimens but not for the natural progesterone group.
  • The most contrasting boyhood behaviors were between those exposed to progesterone and DES. Progesterone subjects tended to recall boyhood behaviors which departed from the conventional male mode toward ‘femininity’. The DES subjects tended to recall the most conventionally ‘masculine’ boyhoods. During adulthood, DES plus natural progesterone subjects reported a high sex drive while synthetic progesterone subjects reported a low sex drive. Erectile failure was more often reported by subjects exposed to natural progesterone only.
  • Three drug regimens were associated with elevations of the Feminine scale of the BSRI and two with elevations of the feminine scale of the GZTS.
  • The rates of homosexual behavior were comparable for drug and non-drug-exposed subjects.
  • The study illustrates that human personality is associated with prenatal hormone exposure.
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As a male, I was prenatally exposed to medically prescribed hormones…

Real Talk with The Cummings and Hugh Easton, 2016

Video published on 12 Apr 2016 by REALTALK W/The Cummings channel with DES Son Hugh Easton.

Can a drug manipulate gender identity?

Listen to what Hugh Easton has to say. We know many DES sons who can confirm that yes, it did happen.

” Among my first discoveries were that I have a type of body structure that’s usually associated with intersex conditions, and that I have symptoms of acute hypogonadism. Basically, my body doesn’t make enough testosterone. Then, I came across a passage in the book “Brain Sex”, about a pattern of very shy, socially withdrawn behaviour that was often seen in teenaged boys who’d been prenatally exposed to an artificial estrogen called DES. It was virtually a perfect match for my own teenage years.

Shortly after that, I joined an online group of DES sons. It was like walking into a disaster zone, with everyone in the group appearing to suffer from health problems of various kinds, including hypogonadism, and various intersex-related abnormalities. One of the first things I noticed was that it was supposed to be a group for DES sons, yet most of the people posting stuff were using women’s names! I later discovered that these people had actually been assigned male at birth… “

More DES DiEthylStilbestrol Resources

Can a Drug manipulate Gender Identity?

Certain doctors and researchers and those in the community believe the DES drug can make a person transgender

Video published on 24 May 2016 by DES Daugther Network channel via Dion Lim 5/6/11pm weeknight anchor/reporter at WTSP/CBS .

It was a pill meant to prevent miscarriages…

Can a drug manipulate gender identity asks Dion Lim?
Well, I know many DES sons who can confirm that yes, it did happen.

More DES DiEthylStilbestrol Resources

Adverse health effects in children of women exposed in utero to diethylstilbestrol

2016 study results confirmed a transgenerational transmission of defects in male genital tract

Abstract

OBJECTIVE
Exposure to diethylstilbestrol (DES) in utero is associated with adverse health effects, including genital anomalies in women and men, and cancers in women. Animal studies showed birth defects and tumors in the offspring of DES exposed mice, revealing transgenerational transmission of DES effects. In humans, birth defects, such as hypospadias were observed in children of prenatally exposed women. The aim of this research was to further assess the health effects in children of prenatally exposed women.

Adverse health effects in children of women exposed in utero to diethylstilbestrol (DES), US National Library of Medicine, NCBI pubmed/27203157, 2016 Feb 5.

Russian doll beauty and the beast, rawdonfox.

METHODS
In a retrospective cohort study, the reports of women exposed to DES in utero on their 4409 children were compared with those of unexposed women on their 6203 children. Comparisons used odd ratios (OR) between children of exposed and unexposed women and standardized incidence rate (SIR) with the general population. These cohorts were recruited on a voluntary basis to answer questionnaires.

RESULTS
There was a global increase of defects in children born to exposed women when compared with those born to unexposed (OR 2.29, 95% CI: 1.80-2.79, P<0.001) and with the general population (SIR 2.39, 95% CI: 2.11-2.68). Increased defects were observed in male genital tract, esophagus, lip or palate, musculoskeletal and circulatory systems. For female genital tract anomalies, there was no significant increase. However, this cohort being relatively young, further follow-up is needed. An increase of cerebral palsy was revealed. The incidence of cancers was not increased, in particular for breast, uterus and ovary.

CONCLUSION
Our results confirmed a transgenerational transmission of defects in male genital tract. With caution due to possible bias associated with this method, our data suggest an increase of defects for esophagus, lip or palate, musculoskeletal and circulatory system in children of exposed women.

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Low-dose and combined effects of oral exposure to BPA and DES on the male reproductive system

Low-dose and combined exposure to BPA and DES may have toxic effects on male fertility in the adult population

Abstract

Study of the joint action of xenobiotics is important to fully explore their toxicity and complete risk analysis. In this study, we investigated the effects of low-dose and combined exposure of Bisphenol-A (BPA) and diethylstilbestrol (DES) on the reproductive system in adult male rats.

The results showed that the sperm motility decreased in the BPA/DES and combined groups. Sperm deformity ratios and histological lesions of the testes were significantly higher and more significant, respectively, in the combined group compared with the single treated groups. No dose-effect relationship or significant additive effect on serum hormone levels was observed after combined exposure to BPA/DES. Ultrastructural results showed lesions of the Sertoli and Leydig cells, mainly in the endoplasmic reticulum (ER), in all treated groups. ER stress molecular sensor IRE1 was phosphorylated and activated after BPA and DES treatment in this study.

Low-dose and combined effects of oral exposure to bisphenol A and diethylstilbestrol on the male reproductive system in adult Sprague-Dawley rats, NCBI pubmed/26970683, doi: 10.1016/j.etap.2016.02.014, 2016 Feb 24.

The protein levels of ES stress molecular marker CHOP were significantly up-regulated after exposure to BPA, DES, and BPA and DES combined.

These findings indicate that ER stress is important in BPA/DES-induced damage in rat testes. Low-dose and combined exposure to BPA and DES may have toxic effects on male fertility in the adult population.

More DES DiEthylStilbestrol Resources