Are the Effects of DES Over? A Tragic Lesson from the Past

Zamora-León, Pilar

doi:10.3390/ijerph181910309

Cited by 22 publications

(11 citation statements)

References 101 publications

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“…We show for the first time that the estrogenic GPER1 activators, E2, BPA, and DES, cause numerical CA triggered by centriole overduplication, leading to karyotype instability in normal colon and CRC cell lines in a GPER1-dependent manner. Given that the sex hormone E2, the well-accepted endocrine-disrupting chemical BPA ( ECHA.eu , ( 30 )), and the known carcinogen DES ( 31 , 32 , 33 ) trigger the evolution of key CRC-prone lesions, our results may provide important clues for a possible role of estrogens in colon pathogenesis and shed light on the underlying mechanism that involves GPER1 function.…”

Section: Introductionmentioning

confidence: 85%

GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

et al. 2022

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The role of the alternate G protein–coupled estrogen receptor 1 (GPER1) in colorectal cancer (CRC) development and progression is unclear, not least because of conflicting clinical and experimental evidence for pro- and anti-tumorigenic activities. Here, we show that low concentrations of the estrogenic GPER1 ligands, 17β-estradiol, bisphenol A, and diethylstilbestrol cause the generation of lagging chromosomes in normal colon and CRC cell lines, which manifest in whole chromosomal instability and aneuploidy. Mechanistically, (xeno)estrogens triggered centrosome amplification by inducing centriole overduplication that leads to transient multipolar mitotic spindles, chromosome alignment defects, and mitotic laggards. Remarkably, we could demonstrate a significant role of estrogen-activated GPER1 in centrosome amplification and increased karyotype variability. Indeed, both gene-specific knockdown and inhibition of GPER1 effectively restored normal centrosome numbers and karyotype stability in cells exposed to 17β-estradiol, bisphenol A, or diethylstilbestrol. Thus, our results reveal a novel link between estrogen-activated GPER1 and the induction of key CRC-prone lesions, supporting a pivotal role of the alternate estrogen receptor in colon neoplastic transformation and tumor progression.

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Section: Introductionmentioning

confidence: 85%

GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

et al. 2022

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“…Diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, is considered the culprit of many somatic disorders in children and grandchildren of mothers treated during pregnancy ( 1 ). It has been estimated that worldwide, ~10 million people have been exposed to DES ( 2 ). However, very few studies investigated DES effects on neurodevelopment and psychiatric disorder occurrence, especially Autism Spectrum Disorders (ASD), in exposed children and their descendants.…”

Section: Introductionmentioning

confidence: 99%

Diethylstilbestrol and autism

et al. 2022

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It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in in-utero exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that in-utero exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in in-utero exposed children (n=1,612), and a French cohort study (n=1,002 in-utero DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in in-utero exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment (ZFP57 and ADAM TS9). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.

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“…Several patients exhibited various reproductive anomalies especially infertility, cysts in uterus, miscarriage. 12 Our previous study demonstrated the successful development of endometriosis by diethylstilbestrol (DES) instead of the traditional surgical induction in the animal model. 13 Further in this study we aimed to prove endometriosis induction of diethylstilbestrol in animal model ensues via immuneinflammatory pathway.…”

Section: Introductionmentioning

confidence: 99%

Evidence Supporting the Diethylstilbestrol Induction of Endometriosis Via Immune-Inflammatory Pathway in Rat Model

Krishnamoorthy

Kadalmani

2022

Int J Life Sci Pharm Res

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Endometriosis is a benign reproductive disorder distinguished by chronic inflammation and anomalous progress of stromal cells and glands outside the uterus. Though the etiology of endometriosis is still a matter of debate, the immuneinflammatory mediators are thought to play a major role. Macrophage infiltration and proinflammatory intermediaries in the peritoneal environment peritoneal milieu impact ovarian, uterine function and pelvic morphology, resulting in endometriosis symptoms and signs. The endometriosis model system was developed using diethylstilbestrol (DES) which is examined to develop the disease via the immune-inflammatory pathway. The immune-inflammatory markers (NFKB, MAPK, TNF-α, IL-6 and STAT- 3) were investigated in this study. The results demonstrated that the DES induced endometriosis animal model had a higher level of CA-125, a biomarker of endometriosis. Endometriosis-induced groups had increased levels of NFKB, MAPK, TNF-α, IL-6 and STAT-3 which clearly depicts the immune-inflammatory role in the induction. Finally, the results conclude that DES induced endometriosis via the immune-inflammatory pathway.

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Are the Effects of DES Over? A Tragic Lesson from the Past

Cited by 22 publications

References 101 publications

GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

Diethylstilbestrol and autism

Evidence Supporting the Diethylstilbestrol Induction of Endometriosis Via Immune-Inflammatory Pathway in Rat Model

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