Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type in a DES-Exposed Woman

American journal of clinical pathology, 2015

Intestinal-metaplasia
Recognition of primary vaginal mucinous adenocarcinoma of intestinal type, extremely rare malignancy, is important, particularly to avoid the pitfall of misdiagnosing metastatic disease.

2015 Study Abstract

OBJECTIVES:
Primary mucinous vaginal adenocarcinoma of intestinal type is an extremely rare malignancy of uncertain histogenesis, which makes for a diagnostic challenge. We report a case and describe the histopathologic features and the unusual immunoprofile of this rare entity.

METHODS:
We report a case of vaginal mucinous adenocarcinoma of intestinal type in a diethylstilbestrol-exposed woman in which intestinal metaplasia of the Skene duct was found at the time of recurrence.

RESULTS:
As the histogenesis of primary vaginal intestinaltype adenocarcinomas remains uncertain, the finding of Skene duct metaplasia in association with invasive adenocarcinoma lends support to the origin of vaginal mucinous adenocarcinomas of intestinal type to be metaplasia, at least in some cases. Such an origin accounts for the unusual immunohistochemical profile, which raises concern for a metastatic adenocarcinoma of gastrointestinal origin.

CONCLUSIONS:
Recognition of this rare entity is important, particularly to avoid the pitfall of misdiagnosing metastatic disease.

Sources and more information
  • Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type, Associated With Intestinal Metaplasia of Skene Ducts in a Diethylstilbestrol-Exposed Woman, American journal of clinical pathology, 2015 Nov;144(5):790-5. doi: 10.1309/AJCPVZ0QNLUO7OFE., NCBI PMID: 26486744.
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159 New Fracking Sites in Yorkshire, the North-West and the East Midlands to be opened up Soon

1,000 sq miles of England to be opened up for fracking

fracking image
Large areas of Yorkshire, the north-west and the east Midlands are to be opened up to fracking after the government announced it will offer a fresh round of licences for oil and gas exploration – 27 new drilling licenses to 12 energy firms, with another 132 licenses expected to come later this year.
Fracking and the future – shale gas in the UK image by Day Donaldson.

This post content was originally published by Common DreamsBreaking News & Views for the Progressive Community

New Fracking Licenses in UK Sound ‘Starting Gun’ of Fight for Climate Future

The UK government on Tuesday handed out dozens of new drilling licenses to energy companies looking to launch fracking operations in the country’s rural areas, just days after officials imbued ministers with new powers to fast-track fossil fuel exploration against residents’ wishes.

The Oil and Gas Authority issued 27 new drilling licenses to 12 energy firms, covering roughly 1,000 square miles of northern UK. Another 132 licenses are expected to come later this year.

From here, the companies will have to apply for drilling permits from local councils. But new rules adopted last week will now make it easier for government officials to step in and approve such bids without waiting for their decisions. That could open up swaths of UK land to harmful and controversial drilling operations like hydraulic fracturing, or fracking, which involves shooting water and chemicals at high pressures into rock formations that hold shale gas.

Climate activists who have been fighting the expansion slammed the issuing of new licenses.

This is the starting gun on the fight for the future of our countryside,” said Daisy Sands, head of Greenpeace UK’s energy campaign. “Hundreds of battles will spring up to defend our rural landscapes from the pollution, noise and drilling rigs that come with fracking.”

Sands also noted that the move comes just weeks after Lancashire County officials rejected a bid by energy firm Cuadrilla to open up a fracking site in the area. Cuadrilla was one of the 12 companies which received a drilling license on Tuesday.

It seems clear that the government is responding to the vigorous lobbying from the fracking companies by ignoring both the economic and environmental evidence that clean, renewable energy is a far better bet for investment and the planet,” Sands said.

Added Andrew Pendleton, head of campaigns at Friends of the Earth UK, “Offering licenses to frack will cause yet more anxiety for people living under the cloud of fracking. The Government is allowing companies to drill right through aquifers that are used to supply household drinking water.”

Sources and more information
  • 1,000 sq miles of England to be opened up for fracking, theguardian, 18 August 2015.
  • New Fracking Licenses in UK Sound ‘Starting Gun’ of Fight for Climate Future, commondreams, August 19, 2015.

Pain Killers in Pregnancy: Prescription Opioid Epidemic and Infant Outcomes

Opioids During Pregnancy Put Babies at Risk

infant image
Infants exposed to opioid pain relievers were more likely to experience a variety of health problems, including low birth weight. Newborns whose pregnant mothers were prescribed opioid drugs may undergo neonatal abstinence syndrome — withdrawal symptoms, essentially. Infants suffering withdrawal may experience breathing problems, convulsions, vomiting, diarrhea, high-pitched crying, poor appetite, jitteriness, tremors, sweating, fever, mottled skin, and excessive sucking or rooting. Image Will Murphy.

2015 Study Abstract

BACKGROUND AND OBJECTIVES:
Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS).

METHODS:
We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics.

RESULTS:
Of 112 029 pregnant women, 31 354 (28%) filled ≥1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67–2.60]) were associated with greater risk of developing NAS.

CONCLUSIONS:
Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.

Sources and More Information
  • Pill-pushing doctors endanger babies by prescribing opioid painkillers to pregnant women, naturalnews, August 15, 2015.
  • Prescription Opioid Epidemic and Infant Outcomes, American Academy of Pediatrics, (doi: 10.1542/peds.2014-3299), February 10, 2015.
  • Drug addict babies: Common pregnancy pain drugs leave newborns suffering horrific withdrawal symptoms, mirror, 14 April 2015.
  • Opioids During Pregnancy Put Babies at Risk, medpagetoday, 04.13.2015.
  • Pregnant Women Prescribed Opioids Have Babies More Likely To Suffer Complications, Withdrawal Symptoms, medicaldaily, Apr 14, 2015.

Signs of epigenetic dysregulation in the autism brain

Hypomethylation of miR-142 promoter and upregulation of microRNAs that target the oxytocin receptor gene in the autism prefrontal cortex

child image
Autism image by hepingting. Study by Bar Ilan University Faculty of Medicine.

2015 Study Abstract

BACKGROUND
MicroRNAs are small RNA molecules that regulate the translation of protein from gene transcripts and are a powerful mechanism to regulate gene networks. Next-generation sequencing technologies have produced important insights into gene transcription changes that occur in the brain of individuals diagnosed with autism spectrum disorder (asd). However, these technologies have not yet been employed to uncover changes in microRNAs in the brain of individuals diagnosed with asd.

METHODS
Small RNA next-generation sequencing was performed on RNA extracted from 12 human autism brain samples and 12 controls. Real-time PCR was used to validate a sample of the differentially expressed microRNAs, and bioinformatic analysis determined common pathways of gene targets. MicroRNA expression data was correlated to genome-wide DNA methylation data to determine if there is epigenetic regulation of dysregulated microRNAs in the autism brain. Luciferase assays, real-time PCR, and Western blot analysis were used to determine how dysregulated microRNAs may regulate the expression and translation of an autism-related gene transcript.

RESULTS
We determined that miR-142-5p, miR-142-3p, miR-451a, miR-144-3p, and miR-21-5p are overexpressed in the asd brain. Furthermore, the promoter region of the miR-142 gene is hypomethylated in the same brain samples, suggesting that epigenetics plays a role in dysregulation of microRNAs in the brain. Bioinformatic analysis revealed that these microRNAs target genes that are involved in synaptic function. Further bioinformatic analysis, coupled with in vitro luciferase assays, determined that miR-451a and miR-21-5p can target the oxytocin receptor (OXTR) gene. OXTR gene expression is increased in these same brain samples, and there is a positive correlation between miR-21-5p and OXTR expression. However, miR-21-5p expression negatively correlates to production of OXTR protein from the OXTR transcript. Therefore, we suggest that miR-21-5p may attenuate OXTR expression in the human autism brain.

CONCLUSIONS
Our data suggests that dysregulation of microRNAs may play a biological role in the brain of individuals of autism. In addition, we suggest an interaction between epigenetic mechanisms and microRNA dysregulation in the brain. Overall, this data adds an important link in our understanding of the molecular events that are dysregulated in the brain of individuals diagnosed with autism.

Sources and More Information
  • Hypomethylation of miR-142 promoter and upregulation of microRNAs that target the oxytocin receptor gene in the autism prefrontal cortex, NCBI PubMed PMID: 26273428, Mol Autism. 2015 Aug 14;6:46. doi: 10.1186/s13229-015-0040-1. eCollection 2015.

L’impact des pesticides sur la santé et le développement des jeunes enfants

Pesticides : “il faut abolir leur utilisation en France”

Le docteur Charles Sultan est endocrinologue et professeur au CHU de Montpellier.
Dérèglements hormonaux, obésité, asthme… il nous explique en quoi les pesticides impactent la santé et le développement des jeunes enfants.

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BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters

Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo

RNA-HOTAIR graphic
Models showing the roles of ERs, MLLs and other ER-coregulators during BPA and DES mediated endocrine disruption of HOTAIR. Steroidogenic EDCs like BPA and DES binds to ERs (ERα and ERβ), in a similar fashion to estradiol. Activated ERs… Image credit NCBI PMC4025971/figure/F7/.

2015 Study Abstract

Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES). Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat. Luciferase assay showed that HOTAIR promoter estrogen-response-elements (EREs) are induced by BPA and DES. Estrogen-receptors (ERs) and ER-coregulators such as MLL-histone methylases (MLL1 and MLL3) bind to the HOTAIR promoter EREs in the presence of BPA and DES, modify chromatin (histone methylation and acetylation) and lead to gene activation. Knockdown of ERs down-regulated the BPA and DES induced expression of HOTAIR. In summary, our results demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo.

It is important to note that, HOTAIR is an antisense transcript and lncRNA. Therefore, our studies also demonstrate that endocrine disruptors can disrupt the noncoding RNAs and can induce antisense transcripts, in a similar fashion as protein coding genes from the sense strands. Our studies revealed novel epigenetic mechanism of endocrine disruption, novel roles of MLL histone methylases and their coordination with ERs and various ER-coregulators during endocrine disruption, both in vitro and in vivo. Although further in vivo analyses are required to understand the detailed mechanism of HOTAIR gene expression and misregulation by EDCs, synthetics estrogens, and other environmental toxins/chemical, our observations indicate that exposure to BPA or DES may turn on the expression of HOTAIR in vivo, in a very similar fashion to estrogen even in the absence of estrogen, and that may result in adverse health effects including cancer and other hormonally regulated disorders.

Sources and more information
  • Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo, J Steroid Biochem Mol Biol. NCBI PMID: 24533973, 2014 May;141:160-70. doi: 10.1016/j.jsbmb.2014.02.002. Epub 2014 Feb 14.
  • Full text NIHMSID: NIHMS569531, PMCID: PMC4025971, 2015 May 1.
DES DiEthylStilbestrol Resources

Intrauterine diethylstilbestrol exposure and increased risk of endometriosis in adulthood

Early-life factors and endometriosis risk

Endometriosis-Awareness-Mon
This 2015 study results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood. Endometriosis Awareness Month image by ALDE Communication.

2015 Study Abstract

OBJECTIVE:
To study early-life factors in relation to endometriosis risk in adulthood.

DESIGN:
Population-based, case-control study. The Women’s Risk of Endometriosis study was conducted among female enrollees aged 18-49 years of a large, integrated healthcare system in western Washington State.

PATIENT(S):
Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population.

MAIN OUTCOME MEASURE(S):
Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstibestrol (DES) exposure, maternal smoking, mother’s age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant’s mother or other family member.

RESULT(S):
We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null.

CONCLUSION(S):
Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.

Sources and more information
  • Early-life factors and endometriosis risk, Upson K, Sathyanarayana S, Scholes D, Holt VL., Fertil Steril. 2015 Jul 23. pii: S0015-0282(15)00469-0. doi: 10.1016/j.fertnstert.2015.06.040, NCBI PMID: 26211883, 2015.
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Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood

Psychiatric disorders evidence from a French cohort of 1002 prenatally DES-exposed children

identity-disorder image
HHORAGES Association work demonstrates that prenatal exposure to DES is associated with a high risk of psychiatric disorders in adolescence and adulthood. Image by JustCallMe_♥Bethy♥.

2015 Study Abstract

In utero diethylstibestrol (DES) exposure has been demonstrated to be associated with somatic abnormalities in adult men and women. Conversely, the data are contradictory regarding the association with psychological or psychiatric disorders during adolescence and adulthood. This work was designed to determine whether prenatal exposure to DES affects brain development and whether it is associated with psychiatric disorders in male and female adolescents and young adults.

HHORAGES Association, a national patient support group, has assembled a cohort of 1280 women who took DES during pregnancy. We obtained questionnaire responses from 529 families, corresponding to 1182 children divided into three groups:

  1. Group 1 (n = 180): firstborn children without DES treatment,
  2. Group 2 (n = 740): exposed children,
  3. and Group 3 (n = 262): children born after a previous pregnancy treated by DES.

No psychiatric disorders were reported in Group 1. In Group 2, the incidence of disorders was drastically elevated (83.8%), and in Group 3, the incidence was still elevated (6.1%) compared with the general population. This work demonstrates that prenatal exposure to DES is associated with a high risk of psychiatric disorders in adolescence and adulthood.

Sources and more information
  • Association between fetal DES-exposure and psychiatric disorders in adolescence/adulthood: evidence from a French cohort of 1002 prenatally exposed children, Soyer-Gobillard MO, Paris F, Gaspari L, Courtet P, Sultan C., NCBI PMID: 26172930, 2015.
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Gene activity and function in the human brain: how enhancers are linked to autism

Brain study reveals insights into genetic basis of autism

Color-and-Shapes
This study is the first to investigate how the activity of enhancers and genes are coordinated in the human brain, and the first to show that brain enhancers are linked to autism. Color and Shapes image by Brian Talbot.

2015 Study Abstract

Despite major progress in identifying enhancer regions on a genome-wide scale, the majority of available data are limited to model organisms and human transformed cell lines.

We have identified a robust set of enhancer RNAs (eRNAs) expressed in the human brain and constructed networks assessing eRNA-gene coexpression interactions across human fetal brain and multiple adult brain regions.

Our data identify brain region–specific eRNAs and show that enhancer regions expressing eRNAs are enriched for genetic variants associated with autism spectrum disorders.

Sources and more information
  • Coexpression networks identify brain region–specific enhancer RNAs in the human brain, Nature Neuroscience, doi:10.1038/nn.4063, 13 July 2015.
  • Brain study reveals insights into genetic basis of autism,
    MedicalXpress, July 13, 2015.

Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women

Reproductive hormone levels in DES-exposed premenopausal women

menopause-lane
In this 2015 study, prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

2015 Study Abstract

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones.

We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders.

DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml – indicators of low ovarian reserve – were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively.

Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

Sources
  • Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women, Wise LA, Troisi R, Hatch EE, Titus LJ, Rothman KJ, Harlow BL, J Dev Orig Health Dis. 2015 Jun;6(3):208-16. doi: 10.1017/S2040174415000082. NCBI PMID: 25698132, Epub 2015 Feb 20. full study.
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