Foetal oestrogens and autism

High Levels of Sex Hormones in The Womb Linked to Autism Once More

A small new study has once again found a link between elevated hormone levels in the womb and the likelihood of developing autism. But this time, instead of major androgens such as testosterone, researchers are pointing the finger at estrogen, medicalxpress and sciencealert report. Image.

Abstract

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

“In conclusion, we have demonstrated that prenatal oestradiol, oestriol and oestrone are elevated in in boys who went on to develop autism. This extends our previous finding of elevated prenatal steroidogenesis in the same cohort and provides further evidence for the prenatal steroid theory of autism. High levels of prenatal oestradiol contribute to a greater degree to autism likelihood than other prenatal sex steroids, including testosterone. We conclude that prenatal oestrogenic excess is a characteristic of autism and may interact with genetic predisposition to affect neurodevelopment.”

See studies in ref to DES and autismADHDDown’s syndrome.

Transgenerational BPA exposure may contribute to autism

Transgenerational Bisphenol A Causes Deficits in Social Recognition and Alters Postsynaptic Density Genes in Mice, 2019

According to a recent mouse study, BPA exposure has transgenerational effects on gene linked to autism – social recognition test used for first time in mice showed behavioral deficit – the Endocrine Society reports.

2019 Study Abstract

Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical. Developmental exposure produces changes in behavior and gene expression in the brain. Here, we examined social recognition behaviors in mice from the third familial generation (F3) after exposure to gestational BPA. Second-generation mice were bred in one of four mating combinations to reveal whether characteristics in F3 were acquired via maternal or paternal exposures. After repeated habituation to the same mouse, offspring of dams from the BPA lineage failed to display increased investigation of a novel mouse. Genes involved in excitatory postsynaptic densities (PSDs) were examined in F3 brains using quantitative PCR. Differential expression of genes important for function and stability of PSDs were assessed at three developmental ages. Several related PSD genes―SH3 and multiple ankyrin repeat domains 1 (Shank1), Homer scaffolding protein 1c (Homer1c), DLG associated protein 1 (Gkap), and discs large MAGUK scaffold protein 4 (PSD95)―were differentially expressed in control- vs BPA-lineage brains. Using a second strain of F3 inbred mice exposed to BPA, we noted the same differences in Shank1 and PSD95 expression in C57BL/6J mice. In sum, transgenerational BPA exposure disrupted social interactions in mice and dysregulated normal expression of PSD genes during neural development. The fact that the same genetic effects were found in two different mouse strains and in several brain regions increased potential for translation. The genetic and functional relationship between PSD and abnormal neurobehavioral disorders is well established, and our data suggest that BPA may contribute in a transgenerational manner to neurodevelopmental diseases.

DES and the GENES

Maternal exposure to workplace solvents may increase the risk for ASD in children

The CHARGE study : an assessment of parental occupational exposures and autism spectrum disorder

Children whose mothers are exposed to solvents at work are at higher risk of autism, shows new research.

The study found that women who are exposed to workplace solvents are 1.5 times more likely to have a child on the autistic spectrum, newnationnews reports. Image credit @ATEN_Int.

2019 Study Abstract

Objectives
The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD).

Methods
Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth.

Results
The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01–2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined.

Conclusion
Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

Impact of male factor infertility on offspring health and development

Long-term health and developmental outcomes in children conceived with intracytoplasmic sperm injection

2019 Study Abstract

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails.

Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately.

In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently.

Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size.

Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls.

Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions.

The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan.

With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.

Reference. Image credit fertilitysmarts.

May Processed Foods Hold Key to Rise in Autism ?

Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder

With the number of children diagnosed with autism on the rise, the need to find what causes the disorder becomes more urgent every day.
UCF researchers are now a step closer to showing the link between the food pregnant women consume and the effects on a fetus’ developing brain.

2019 Study Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by glia over-proliferation, neuro-inflammation, perturbed neural circuitry, and gastrointestinal symptoms. The role of gut dys-biosis in ASD is intriguing and should be elucidated.

We investigated the effect of Propionic acid (PPA), a short-chain fatty acid (SCFA) and a product of dys-biotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation and inflammation.

hNSCs proliferated to 66 neuropsheres when exposed to PPA versus 45 in control. The neurosphere diameter also increased at day 10 post PPA treatment to (Mean: 193.47 um ± SEM: 6.673 um) versus (154.16 um ± 9.95 um) in control, p < 0.001. Pre-treatment with β-HB, SCFA receptor inhibitor, hindered neurosphere expansion (p < 0.001). While hNSCs spontaneously differentiated to (48.38% ± 6.08%) neurons (Tubulin-IIIβ positive) and (46.63% ± 2.5%) glia (GFAP positive), PPA treatment drastically shifted differentiation to 80% GFAP cells (p < 0.05). Following 2 mM PPA exposure, TNF-α transcription increased 4.98 fold and the cytokine increased 3.29 fold compared to control (P < 0.001). Likewise, GPR41 (PPA receptor) and pro-survival p-Akt protein were elevated (p < 0.001). PTEN (Akt inhibitor) level decreased to (0.42 ug/ul ± 0.04 ug/ul) at 2 mM PPA compared to (0.83 ug/ul ± 0.09 ug/ul) in control (p < 0.001). PPA at 2 mM decreased neurite outgrowth to (80.70 um ± 5.5 um) compared to (194.93 um ± 19.7 um) in control.

Clearly, the data supports a significant role for PPA in modulating hNSC patterning leading to gliosis, disturbed neuro-circuitry, and inflammatory response as seen in ASD.

Behavioral disorders in kids with autism linked to reduced brain connectivity

Reduced Amygdala–Prefrontal Functional Connectivity in Children With Autism Spectrum Disorder and Co-occurring Disruptive Behavior

Reduced connectivity between the amygdala and ventrolateral prefrontal cortex has been identified in children on the autism spectrum who exhibit disruptive behaviors, compared to those on the spectrum who do not. Findings suggest this distinct brain network could be independent of core autism symptoms.

More than a quarter of children with autism spectrum disorder are also diagnosed with disruptive behavior disorders. For the first time, Yale researchers have identified a possible biological cause: a key mechanism that regulates emotion functions differently in the brains of the children who exhibit disruptive behavior.

Neuroscience News reports, 21/04/2019.

2019 Study Abstract

Background

Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity.

Methods

This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses.

Results

Children with ASD and disruptive behavior showed reduced amygdala–vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects.

Conclusions

Reduced amygdala–vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Screening for rare epigenetic variations in autism and schizophrenia

Additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders

2019 Study Abstract

While many studies have led to the identification of rare sequence variants linked with susceptibility to autism and schizophrenia, the contribution of rare epigenetic variations (epivariations) in these disorders remains largely unexplored.

Previously we presented evidence that epivariations occur relatively frequently in the human genome, and likely contribute to a subset of congenital and neurodevelopmental disorders through the disruption of dosage-sensitive genes.

Here we extend this approach, studying methylation profiles from 297 samples with autism and 767 cases with schizophrenia, identifying 84 and 268 rare epivariations in these two cohorts, respectively, that were absent from 4,860 population controls.

We observed multiple features associated with these epivariations that support their pathogenic relevance, including

  1. a significant enrichment for epivariations in schizophrenic individuals at genes previously linked with schizophrenia,
  2. increased brain expression of genes associated with epivariations found in autism cases compared with controls,
  3. in autism families, a significant excess of epivariations found specifically in affected versus unaffected sibs,
  4. Gene Ontology terms linked with epivariations found in autism, including “D1 dopamine receptor binding.”

Our study provides additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders. Image credit Brigham and Women’s Hospital.

DES DIETHYLSTILBESTROL RESOURCES

DES Transgenerational Neurodevelopmental Deficits, 2018 Study

Collaborative on Health and the Environment Webinar, 20 March 2019

Dr. Marianthi-Anna Kioumourtzoglou, Assistant Professor in the Department of Environmental Health Sciences at Columbia University Mailman School of Public Health, describes the study Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits design, statistical analyses, and findings.

References

DES DIETHYLSTILBESTROL RESOURCES

Vaxxed: From Cover-Up to Catastrophe

Doctor behind film that links autism to vaccines speaks out featuring Dr. Andrew Wakefield & Polly Tommey

A 2016 American film alleging a cover-up by the Centers for Disease Control and Prevention (CDC) of a purported link between the MMR vaccine and autism.

Official site.

EU should ban brain-harming chlorpyrifos to protect health

Exposure to chlorpyrifos is linked to ADHD and autism. It should not be allowed on the European market

Today, the Health and Environment Alliance (HEAL) together with Générations Futures, Pesticide Action Network Europe and Pesticide Action Network Germany released a factsheet on the health effects of chlorpyrifos.

Chlorpyrifos is one of the most widely used pesticides in Europe and its residues are also commonly found in our food. The current authorisation for chlorpyrifos on the European market will expire on 31 January 2019. We are very concerned about the possibility of an extended authorisation due to its health harming properties. Chlorpyrifos is linked to the disruption of the hormonal system and effects on the developing human brain. Children exposed to chlorpyrifos in the womb or in early life can suffer neurodevelopmental effects later in life, like attention deficit disorders (ADHD) and autism.

This factsheet sets out the case and evidence against the use of chlorpyrifos and explains the health impacts which justify its ban.

Reference.