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.

Chlorpyrifos : another pesticide that must be banned

The EU approval of the brain-damaging pesticide chlorpyrifos was based on one single biased study – commissioned by industry…

The Cross-border investigation on chlorpyrifos was initiated by Investigative Reporting Denmark and Danwatch, and made in collaboration with journalists from Knack in Belgium, Le Monde in France, Dagbladet in Norway, Newsweek in Poland, Ostro in Slovenia, El Confidential in Spain and The Midwest Center for Investigative Reporting in US. The investigation was supported by Journalismfund.eu.

Environmental Chemicals and Autism

A Scoping Review of the Human and Animal Research, 2019

The Endocrine Disruption Exchange newest scoping review finds that 152 environmental chemicals have been investigated in humans or animals for their association with autism. TEDX highlight the need for systematic review of lead, PCBs, and chlorpyrifos.

Abstract

Background
Estimates of autism prevalence have increased dramatically over the past two decades. Evidence suggests environmental factors may contribute to the etiology of the disorder.

Objectives
This scoping review aimed to identify and categorize primary research and reviews on the association between prenatal and early postnatal exposure to environmental chemicals and the development of autism in epidemiological studies and rodent models of autism.

Methods
PubMed was searched through 8 February 2018. Included studies assessed exposure to environmental chemicals prior to 2 months of age in humans or 14 d in rodents. Rodent studies were considered relevant if they included at least one measurement of reciprocal social communicative behavior or repetitive and stereotyped behavior. Study details are presented in interactive displays using Tableau Public.

Results
The search returned 21,603 unique studies, of which 54 epidemiological studies, 46 experimental rodent studies, and 50 reviews were deemed relevant, covering 152 chemical exposures. The most frequently studied exposures in humans were particulate matter (n=14), mercury (n=14), nonspecific air pollution (n=10), and lead (n=10). In rodent studies, the most frequently studied exposures were chlorpyrifos (n=9), mercury (n=6), and lead (n=4).

Discussion
Although research is growing rapidly, wide variability exists in study design and conduct, exposures investigated, and outcomes assessed. Conclusions focus on recommendations to guide development of best practices in epidemiology and toxicology, including greater harmonization across these fields of research to more quickly and efficiently identify chemicals of concern. In particular, we recommend chlorpyrifos, lead, and polychlorinated biphenyls (PCBs) be systematically reviewed in order to assess their relationship with the development of autism. There is a pressing need to move forward quickly and efficiently to understand environmental influences on autism in order to answer current regulatory questions and inform treatment and prevention efforts.

60 MiNueTs Toxic

UCSF Program on Reproductive Health and the Environment, 2017

Video published on 18 Apr 2019 by the UCSF Program on Reproductive Health and the Environment.

The University of California San Francisco (UCSF) Program on Reproductive Health and the Environment (PRHE)’s mission is to create a healthier environment for human reproduction and development through advancing scientific inquiry, clinical care and health policies that prevent exposures to harmful chemicals in our environment.

More Information

Why are ObGyns Talking Toxins ?

Let’s make environmental health part of health care

Doctors from 125 countries want policies to prevent exposure to toxic chemicals

Produced for PRHE by Susan Lamontagne, Public Interest Media Group, for the International Federation of Gynecology and Obstetrics (FIGO) XXI World Congress on September 30, 2015.

Why are Doctors Talking Toxins ?

And how to reduce exposure to toxic chemicals worldwide ?

It’s time to shift the burden of proof, from scientists, back to the chemical industry

Video published on 5 June 2019, by UCSF Program on Reproductive Health and the Environment.