Exposure to BPA during pregnancy may cause health problems for offspring

Bisphenol A -- BPA -- used in plastic packaging and in the linings of food and beverage cans, may be passed from a mother to her offspring during pregnancy and cause changes in the gut bacteria of the offspring, according to an international team of researchers.
In a study on rabbits, the researchers observed that exposure to BPA during pregnancy caused chronic inflammation in the offspring's intestines and liver. The researchers also noted signs of increased gut permeability -- or leaky gut -- and a decrease in the diversity of gut bacteria and anti-inflammatory bacterial metabolites, such as short-chain fatty acids, said Jairam K.P. Vanamala, associate professor of food sciences, Penn State.
Leaky gut and decreased gut-bacteria diversity and metabolites are considered biomarkers -- or indicators -- of inflammation-related chronic diseases, he added.
"Obesity and inflammation-promoted chronic diseases like colon cancer and type 2 diabetes are increasing not just in America, but worldwide," said Vanamala. "We know that many types of cancers are inflammation-promoted, like colon cancer. But, we have not understood what causes inflammation in the intestine and liver. We have previously shown that food is a double-edge sword. Some foods can promote inflammation in the intestine, whereas bright-colored fruits and vegetables, like purple potatoes, can suppress intestinal inflammation. This study shows that we also need to think about the toxins in the environment."

What does the environment have to do with autism? | Ensia

Prenatal bisphenol A exposure weakens body's fullness cues

The new study found mice born to mothers exposed to bisphenol A were less responsive to the hormone leptin, which is sometimes called the satiety hormone. Leptin helps inhibit the appetite by reducing hunger pangs when the body does not need energy. The hormone sends signals to the hypothalamus region of the brain to suppress the appetite.
"Our findings show that bisphenol A can promote obesity in mice by altering the hypothalamic circuits in the brain that regulate feeding behavior and energy balance," said the study's senior author, Alfonso Abizaid, Ph.D., of the Department of Neuroscience at Carleton University in Ottawa, Canada. "Low level prenatal exposure to BPA delays a surge of leptin after birth that allows mice to develop the proper response to the hormone. BPA exposure permanently alters the neurobiology in the affected mice, making them prone to obesity as adults.



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The consumption of canned food and beverages and urinary Bisphenol A concentrations in NHANES 2003–2008

Background
Exposure to Bisphenol A (BPA) is ubiquitous and includes dietary and environmental pathways. BPA is rapidly glucuronidated in the body, and both BPA and its conjugates can be readily measured in urine.
Objectives
To investigate the contribution of canned food and beverages, known sources of BPA contamination, to BPA biomarkers of exposure using dietary and urinary BPA concentration information in a representative sample of the U.S. population.
Methods
We evaluated 7669 NHANES 2003–2008 participants 6 years and older with 24-h dietary recall information and urinary BPA concentrations available. Using linear regression models, we evaluated the associations between recent canned food and beverage consumption and urinary BPA concentrations, adjusting for potential confounders.
Results
We found 9% of our participants consumed one canned food in the past 24 h and 2% consumed two or more canned foods. The consumption of one canned food vs. none was associated with 24% (95% CI 1.11, 1.38) higher urinary BPA concentrations. The consumption of two or more canned foods vs. none was associated with 54% (95% CI 1.27, 1.88) higher urinary BPA concentrations. The consumption of one or more of some specific types of canned foods vs. none were associated with higher urinary BPA concentrations: 41% (95% CI 1.23, 1.63) higher BPA for vegetable and fruit, 70% (95% CI 1.18, 2.44) higher for canned pasta, and 229% (95% CI 1.22, 4.30) higher for canned soup. Canned beverages were not associated with urinary BPA concentrations.
Conclusions
Canned food, including some specific types such as canned vegetable and fruit, canned pasta, and canned soup were associated with higher levels of urinary BPA concentrations."

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes

Even taking problems of diagnosis into account, a five-fold increase in the incidence of autism in recent decades, in the absence of any known changes in the human gene pool suggests a strong environmental influence. Numerous pollutants have been implicated in epidemiological studies, including pesticides, heavy metals, industrial solvents, air pollutants, particulate matter, bisphenol A, phthalates and flame retardants. Many genes have been implicated in autism, some of which are directly related to detoxification processes. Many are also expressed prenatally in the frontal cortex when the effects of such toxins on neurodevelopment are most relevant. To gain access to the foetal brain, toxins must pass placental and blood/brain barriers and access to maternal or children's blood necessitates passage across skin, airway and intestinal barriers. Literature survey of a subset of 206 genes, defined as prime autism susceptibility candidates from an Autworks/Genotator analysis, revealed that most could be related to barrier function at blood/brain, skin, intestinal, placental or other interfaces. These genes were highly enriched in proteome datasets from blood/brain and placental trophoblast barriers and many localised to skin, intestinal, lung, umbilical and placental compartments. Many were also components of the exosomal/transcytosis pathway that is involved in the transfer of compounds across cells themselves, rather than between them. Several are involved in the control of respiratory cilia that sweep mucus and noxious particles from the airways. A key role of autism susceptibility genes may thus relate to their ability to modulate the access of numerous toxins to children, and adults and, during gestation, to the developing foetal brain.

BPA exposure linked to autism spectrum disorder, study reports -- ScienceDaily

 "Newly published study is the first to report an association between bisphenol-A (BPA), a common plasticizer used in a variety of consumer food and beverage containers, with autism spectrum disorder (ASD) in children. The study, by researchers at Rowan University School of Osteopathic Medicine (RowanSOM) and Rutgers New Jersey Medical School (NJMS), shows that BPA is not metabolized well in children with ASD."



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BPA exposure during pregnancy causes oxidative stress in child, mother

"Researchers analyzed blood samples from 24 mother and infant pairs to examine the effects of BPA exposure. The women had blood drawn during the first trimester of pregnancy to measure their BPA levels. The women were divided into two groups - those who had lower levels of BPA in their blood, and those who had higher levels. Researchers also took blood samples from the umbilical cords after the babies were delivered and measured the amount of chemical byproducts created by oxidative stress.
The blood analysis revealed that the human mothers exposed to higher levels of BPA and their infants showed signs of oxidative stress caused by overexposure to nitric oxide-derived free radicals. The study participants had larger amounts of byproducts caused by this type of oxidative damage in their blood.
In addition to the human subjects, the researchers studied the effects of BPA on pregnancy in sheep, rats and mice. The scientists fed animals diets containing either high or low doses of BPA. The researchers then measured the resulting oxidative stress on the mothers and their offspring using blood samples. The results corroborated the results in the human study."

BPA and BPS affect embryonic brain development in zebrafish

Bisphenol A, known as BPA, is produced in massive quantities around the world for use in consumer products, including household plastics. In response to public concerns, many manufacturers have replaced BPA with a chemical called bisphenol S (BPS), which is often labeled as "BPA-free" and presumed to be safer.
In a study published Monday, Jan. 12, in the Proceedings of the National Academy of Sciences (PNAS), researchers in Deborah Kurrasch's lab at the University of Calgary have provided evidence that BPA and BPS cause alterations in brain development leading to hyperactivity in zebrafish.
Researchers discovered the number of neurons generated in the developing zebrafish brains increased by 180 per cent compared with unexposed fish. They also learned that BPS increased the number of neurons by 240 per cent in similar experiments. The result was a change in behaviour, with the fish demonstrating greater hyperactivity later in life.
Another surprise finding was that zebrafish receptors targeted by BPA and BPS to mediate this early neuronal birth in zebrafish brains were androgen receptors. Assumptions based on numerous reports postulated that BPA and BPS modulate normal physiology by mimicking the endogenous sex steroid estrogen, and not testosterone.

Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals.

Humans are increasingly and consistently exposed to a variety of
endocrine disrupting chemicals (EDCs), chemicals that have been linked
to neurobehavioral disorders such as ADHD and autism.
Many of such EDCs have been shown to adversely influence brain
mesocorticolimbic systems raising the potential for cumulative toxicity.
As such, understanding the effects of developmental exposure to
mixtures of EDCs is critical to public health protection. Consequently,
this study compared the effects of a mixture of four EDCs to their
effects alone to examine potential for enhanced toxicity, using
behavioral domains and paradigms known to be mediated by
mesocorticolimbic circuits (fixed interval (FI) schedule controlled
behavior, novel object recognition memory and locomotor activity) in
offspring of pregnant mice that had been exposed to vehicle or
relatively low doses of four EDCs, atrazine (ATR - 10mg/kg),
perfluorooctanoic acid (PFOA - 0.1mg/kg), bisphenol-A (BPA - 50μg/kg),
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - 0.25μg/kg) alone or combined
in a mixture (MIX), from gestational day 7 until weaning. EDC-treated
males maintained significantly higher horizontal activity levels across
three testing sessions, indicative of delayed habituation, whereas no
effects were found in females. Statistically significant effects of MIX
were seen in males, but not females, in the form of increased FI
response rates, in contrast to reductions in response rate with ATR, BPA
and TCDD, and reduced short term memory in the novel object recognition
paradigm. MIX also reversed the typically lower neophobia levels of
males compared to females. With respect to individual EDCs, TCDD
produced notable increases in FI response rates in females, and PFOA
significantly increased ambulatory locomotor activity in males.
Collectively, these findings show the potential for enhanced behavioral
effects of EDC mixtures in males and underscore the need for animal
studies to fully investigate mixtures, including chemicals that converge
on common physiological substrates to examine potential mechanisms of
toxicity with full dose effect curves to assist in interpretations of
relevant mechanisms.

BPA exposure by infants may increase later risk of food intolerance

If it seems like more people are allergic to, or intolerant of, more and
different kinds of foods than ever before, there might be a reason why.
A new research published in November 2014 issue of The FASEB Journal,
scientists show, for the first time, that there is a link between
perinatal exposure to Bisphenol A (BPA) at low doses and the risk to
develop food intolerance in later life. This research involving rats
suggests that early life exposure at a dose significantly below the
current human safety limit set by the FDA affects developing immune
systems, predisposing offspring to food intolerance in adulthood.

BPA may affect the developing brain by disrupting gene regulation

Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations.

Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

Bisphenol a inhibits voltage-activated Ca2+ channels in vitro: mechanisms and structural requirements.

Bisphenol A (BPA), a high volume production chemical compound attracts growing attention as a health-relevant xenobiotic in humans. It can directly bind to hormone receptors, enzymes, and ion channels to become biologically active. In this study we show that BPA acts as a potent blocker of voltage-activated Ca(2+) channels. We determined the mechanisms of block and the structural elements of BPA essential for its action. Macroscopic Ba(2+)/ Ca(2+) currents through native L-, N-, P/Q-, T-type Ca(2+) channels in rat endocrine GH(3) cells, mouse dorsal root ganglion neurons or cardiac myocytes, and recombinant human R-type Ca(2+) channels expressed in human embryonic kidney (HEK) 293 cells were rapidly and reversibly inhibited by BPA with similar potency (EC(50) values: 26-35 μM). Pharmacological and biophysical analysis of R-type Ca(2+) channels revealed that BPA interacts with the extracellular part of the channel protein. Its action does not require intracellular signaling pathways, is neither voltage- nor use-dependent, and does not affect channel gating. This indicates that BPA interacts with the channel in its resting state by directly binding to an external site outside the pore-forming region. Structure-effect analyses of various phenolic and bisphenolic compounds revealed that 1) a double-alkylated (R-C(CH(3))(2)-R, R-C(CH(3))(CH(2)CH(3))-R), or double-trifluoromethylated sp(3)-hybridized carbon atom between the two aromatic rings and 2) the two aromatic moieties in angulated orientation are optimal for BPA's effectiveness. Since BPA highly pollutes the environment and is incorporated into the human organism, our data may provide a basis for future studies relevant for human health and development.


Perhaps relevant to numerous channelopathies.

Researchers discover adverse effects of Bisphenol A on calcium channels

(Medical Xpress)—Bisphenol A, a substance found in many synthetic products, is considered to be harmful, particularly, for fetuses and babies. Researchers from the University of Bonn have now shown in experiments on cells from human and mouse tissue that this environmental chemical blocks calcium channels in cell membranes. Similar effects are elicited by drugs used to treat high blood pressure and cardiac arrhythmia. The results are now presented in the journal Molecular Pharmacology.

Read more at: http://medicalxpress.com/news/2012-12-adverse-effects-bisphenol-calcium-channels.html#jCp'

Study shows BPA exposure in fetal livers

ScienceDaily (Dec. 3, 2012) — New research from the University of Michigan School of Public Health found BPA, or bisphenol A, in fetal liver tissue, demonstrating that there is considerable exposure to the chemical during pregnancy.

BPA shown to disrupt thyroid function in pregnant animals and offspring

In utero exposure to bisphenol A (BPA) can be associated with decreased thyroid function in newborn sheep, according to a recent study accepted for publication in Endocrinology. Hypothyroidism is characterized by poor mental and physical performance in human adults and in children can result in cognitive impairment and failure to grow normally.

Read more at: http://medicalxpress.com/news/2012-11-bpa-shown-disrupt-thyroid-function.html#jCp

Toxicology: The learning curve : Nature News & Comment: Toxic effects of low doses

Endocrine disrupters include a large group of synthetic chemicals that interact with cellular hormone receptors. These compounds, which range from the common weed killer atrazine and the plasticizer bisphenol A (BPA) to the antibacterial agent triclosan (used in cleansers) and the vineyard fungicide vinclozolin, don't play by the usual rules of toxicology. On the basis of conventional high-dose testing, regulators have set maximum acceptable levels for each of them that assume all doses below that level are safe. But academic researchers who have studied a wider range of doses, including very low ones found in the everyday environment, say that their experiments usually do not generate the tidy, familiar 'ski-slope' dose-response graphs of classic toxicology. Instead, most endocrine disrupters have 'non-monotonic' dose-response curves, meaning that their slopes change at least once from negative to positive, or vice versa, forming 'U' shapes, inverted 'U's or even stranger shapes that resemble undulating Chinese dragons. 

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