Common Herbicide May Devastate Future Generations

Common Herbicide May Devastate Future Generations

The study provides evidence that glyphosate-induced changes to exposed rats could be used as biomarkers for determining propensity in subsequent generations for prostate and kidney diseases as well as obesity and incurring multiple diseases at once. In fact, by the time third- and fourth-generation rats whose predecessors had been exposed to the chemical were middle-aged, 90% had one or more of these health problems, a dramatically higher rate than the control group.

Epigenome-wide association study for glyphosate induced transgenerational xxxxx DNA methylation and histone retention epigenetic biomarkers for disease

https://www.tandfonline.com/doi/full/10.1080/15592294.2020.1853319

#glyphosate #herbicide #epigenome

Glyphosate, herbicide, transgenerational, histone, DNA methylation, prostate, kidney, obesity, epigenetic transgenerational inheritance of pathology, toxicology, pesticide, organic, generation, diagnostic tests, germline epimutation, include imprinted-like gene characteristics

Nutrient in Eggs and Meat May Influence Gene Expression from Infancy to Adulthood: Choline

 

 

Implications for Wide Range of Disorders – Hypertension to Mental Health Problems

 

September 20, 2012

 

Just as women are advised to get plenty of folic acid around the time of conception and throughout early pregnancy, new research suggests another very similar nutrient may one day deserve a spot on the obstetrician’s list of recommendations.

 

Consuming greater amounts of choline – a nutrient found in eggs and meat – during pregnancy may lower an infant’s vulnerability to stress-related illnesses, such as mental health disturbances, and chronic conditions, like hypertension, later in life.

 

In an early study in The FASEB Journal, nutrition scientists and obstetricians at Cornell University and the University of Rochester Medical Center found that higher-than-normal amounts of choline in the diet during pregnancy changed epigenetic markers – modifications on our DNA that tell our genes to switch on or off, to go gangbusters or keep a low profile – in the fetus. While epigenetic markers don’t change our genes, they make a permanent imprint by dictating their fate: If a gene is not expressed – turned on – it’s as if it didn’t exist.

 

The finding became particularly exciting when researchers discovered that the affected markers were those that regulated the hypothalamic-pituitary-adrenal or HPA axis, which controls virtually all hormone activity in the body, including the production of the hormone cortisol that reflects our response to stress and regulates our metabolism, among other things.

 

More choline in the mother’s diet led to a more stable HPA axis and consequently less cortisol in the fetus. As with many aspects of our health, stability is a very good thing: Past research has shown that early exposure to high levels of cortisol, often a result of a mother’s anxiety or depression, can increase a baby’s lifelong risk of stress-related and metabolic disorders.

 

“The study is important because it shows that a relatively simple nutrient can have significant effects in prenatal life, and that these effects likely continue to have a long-lasting influence on adult life,” said Eva K. Pressman, M.D., study author and director of the high-risk pregnancy program at the University of Rochester Medical Center. “While our results won’t change practice at this point, the idea that maternal choline intake could essentially change fetal genetic expression into adulthood is quite novel.”

 

Pressman, who advises pregnant women every day, says choline isn’t something people think a lot about because it is already present in many things we eat and there is usually no concern of choline deficiency. Though much more research has focused on folate – functionally very similar to choline and used to decrease the risk of neural tube defects like spina bifida – a few very compelling studies sparked her interest, including animal studies on the role of choline in mitigating fetal alcohol syndrome and changing outcomes in Down syndrome.

 

A long-time collaborator with researchers at Cornell, Pressman joined a team led by Marie Caudill, Ph.D., R.D., professor in the Division of Nutritional Sciences at Cornell, in studying 26 pregnant women in their third trimester who were assigned to take 480 mg of choline per day, an amount slightly above the standard recommendation of 450 mg per day, or about double that amount, 930 mg per day. The choline was derived from the diet and from supplements and was consumed up until delivery.

 

The team found that higher maternal choline intake led to a greater amount of DNA methylation, a process in which methyl groups – one carbon atom linked to three hydrogen atoms – are added to our DNA. Choline is one of a handful of nutrients that provides methyl groups for this process. The addition of a single methyl group is all it takes to change an individual’s epigenome.

 

Measurements of cord blood and samples from the placenta showed that increased choline, via the addition of methyl groups, altered epigenetic markers that govern cortisol-regulating genes. Higher choline lessened the expression of these genes, leading to 33 percent lower cortisol in the blood of babies whose mom’s consumed 930 mg per day.

 

Study authors say the findings raise the exciting possibility that choline may be used therapeutically in cases where excess maternal stress from anxiety, depression or other prenatal conditions might make the fetal HPA axis more reactive and more likely to release greater-than-expected amounts of cortisol.

 

While more research is needed, Caudill says that her message to pregnant women would be to consume a diet that includes choline rich foods such as eggs, lean meat, beans and cruciferous vegetables like broccoli. For women who limit their consumption of animal products, which are richer sources of choline than plant foods, she adds that supplemental choline may be warranted as choline is generally absent in prenatal vitamin supplements.

 

“One day we might prescribe choline in the same way we prescribe folate to all pregnant women,” notes Pressman, the James R. Woods Professor in the Department of Obstetrics and Gynecology. “It is cheap and has virtually no side effects at the doses provided in this study. In the future, we could use choline to do even more good than we are doing right now.”

 

In addition to Pressman and Caudill, several scientists and clinicians from the Division of Nutritional Science and the Statistical Consulting Unit at Cornell and the Cayuga Medical Center in Ithaca, N. Y., participated in the research. The study was funded by the Egg Nutrition Center, the National Cattlemen’s Beef Association, the Nebraska Beef Council, the U.S. Department of Agriculture and the President’s Council of Cornell Women. The funding sources had no role in the study design, interpretation of the data, or publication of the results.

 

 

 

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The epigenetics of increasing weight through the generations ” resulting in amplification of obesity across generations “

Re-Post from 2008

Contact: Dipali Pathak
pathak@bcm.edu
713-798-4710
Baylor College of Medicine

Overweight mothers give birth to offspring who become even heavier, resulting in amplification of obesity across generations, said Baylor College of Medicine researchers in Houston who found that chemical changes in the ways genes are expressed – a phenomenon called epigenetics — could affect successive generations of mice.

“There is an obesity epidemic in the United States and it’s increasingly recognized as a worldwide phenomenon,” said Dr. Robert A. Waterland, assistant professor of pediatrics – nutrition at BCM and lead author of the study that appears in the International Journal of Obesity. “Why is everyone getting heavier and heavier? One hypothesis is that maternal obesity before and during pregnancy affects the establishment of body weight regulatory mechanisms in her baby. Maternal obesity could promote obesity in the next generation.”

Waterland and his colleagues studied the effect of maternal obesity in three generations of genetically identical mice, all with the same genetic tendency to overeat. One group of mice received a standard diet; the other a diet supplemented with the nutrients folic acid, vitamin B12, betaine and choline. The special ‘methyl supplemented’ diet enhances DNA methylation, a chemical reaction that silences genes.

“We wanted to know if, even among genetically identical mice, maternal obesity would promote obesity in her offspring, and if the methyl supplemented diet would affect this process,” said Waterland. “Indeed, those on the regular diet got fatter and fatter with each generation. Those in the supplemented group, however, did not.”

“We think DNA methylation may play an important role in the development of the hypothalamus (the region of the brain that regulates appetite),” said Waterland.

“Twenty years ago, it was proposed that just as genetic mutations can cause cancer, so too might aberrant epigenetic marks – so called ‘epimutations.’ That idea is now largely accepted and the field of cancer epigenetics is very active. I would make the same statement for obesity. We are on the cusp of understanding that,” he said.

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Waterland is also a researcher at the USDA/ARS Children’s Nutrition Research Center at BCM and Texas Children’s Hospital. Others who contributed to this research include Kajal Tahiliani, Marie-Therese Rached and Sherin Mirza of Baylor College of Medicine and the USDA/ARS Children’s Nutrition Research Center in Houston and Michael Travisano of the University of Minnesota in St. Paul.

Funding for this work came from the National Institutes of Health, the March of Dimes Birth Defects Foundation and the U.S. Department of Agriculture.

When the embargo lifts, this report is available at the website of the http://www.nature.com/ijo/index.html.

For more information on basic science research at Baylor College of Medicine, please go to http://www.bcm.edu/fromthelab/.

Common flame retardant linked to social, behavioral and learning deficits

Study highlights the interaction between epigenetics and genetics and exposure to a flame retardant in mice

Mice genetically engineered to be susceptible to autism-like behaviors that were exposed to a common flame retardant were less fertile and their offspring were smaller, less sociable and demonstrated marked deficits in learning and long-term memory when compared with the offspring of normal unexposed mice, a study by researchers at UC Davis has found. The researchers said the study is the first to link genetics and epigenetics with exposure to a flame retardant chemical.

The research was published online today in the journal Human Molecular Genetics. It will be presented during a symposium on Saturday, Feb. 18, at the annual meeting of the American Association for the Advancement of Science (AAAS) by Janine LaSalle, a professor in the Department of Medical Microbiology and Immunology in the UC Davis School of Medicine and the UC Davis Genome Center. (LaSalle will discuss her research during a news briefing with other autism researchers at 9 a.m. on Feb. 19 in Room 221 on the second Level of the Vancouver Convention Center).

“This study highlights the interaction between epigenetics and the effects of early exposure to flame retardants,” said Janine LaSalle, the study’s senior author and a researcher affiliated with the UC Davis MIND Institute. “Our experiments with wild-type and mutant mice indicate that exposure to flame retardants presents an independent risk of neurodevelopmental deficits associated with reduced sociability and learning.”

Epigenetics describes the heritable changes in gene expression caused by mechanisms other than those in the DNA sequence. One such mechanism is DNA methylation, in which genes are silenced when their activation no longer is required. DNA methylation is essential for normal development. The researchers chose a mouse that was genetically and epigenetically susceptible to social behavioral deficits in order to understand the potential effect of this environmental pollutant on genetically susceptible humans.

LaSalle and her colleagues examined the effects of the chemical BDE-47 (Tetrabromodiphenl ether), a member of the class of flame retardants called polybrominated diphenylethers, or PBDEs. PBDEs have been used in a wide range of products, including electronics, bedding, carpeting and furniture.  They have been shown to persist in the environment and accumulate in living organisms, and toxicological testing has found that they may cause liver toxicity, thyroid toxicity and neurodevelopmental toxicity, according to U.S. Environmental Protection Agency. BDE-47 is the PBDE found at highest concentrations in human blood and breast milk, raising concerns about its potential neurotoxic effects during pregnancy and neonatal development.

The research was conducted in the offspring of mice genetically engineered for the autism phenotype found in Rett syndrome, a disorder that occurs primarily in females and causes regression in expressive language, motor skills and social reciprocity in late infancy. The condition affects about 1 in 10,000 children.

Autism spectrum disorders are a group of neurodevelopmental disabilities that can cause significant social, communication and behavioral deficits. The U.S. Centers for Disease Control and Prevention estimates that an average of 1 in 110 children born in the United States today will be diagnosed with an autism spectrum disorder.

Rett syndrome is causally linked to defects in the methyl-CpG-binding protein 2 gene MECP2 situated on the X chromosome. Mutations in MECP2 result in a nonfunctional MeCP2 protein, which is required for normal brain development. The researchers evaluated the effects of exposure to BDE-47 on mice genetically engineered to have mutations in MECP2 and their offspring, or pups. The genetically engineered Mecp2 mother mice, or dams, were bred with non-mutant wild-type males. The dams were monitored for 10 weeks — for four weeks prior to conception, three weeks during gestation and three weeks of lactation. They were then compared with a control group of normal, unexposed dams and pups over several generations and hundreds of mice.

The study found that that the weights of the pups of the lactating BDE-47-exposed dams were diminished when compared with the controls, as were their survival rates. To assess the effects of the flame retardant exposure on the pups and their genotypes, the researchers placed them through more than 10 cognitive, social and physical tests.

Female offspring of dams exposed with BDE-47 spent half as much time interacting with another mouse in a 10-minute sociability test compared to controls. The reduced sociability in BDE-47 exposed females corresponded to reduced DNA methylation in females regardless of genotype.  In addition, genetic and environmental interaction effects in this study were specifically observed in females.

In a short-term memory test of social novelty, although all mice showed the expected preference for interacting with a novel over a familiar mouse, BDE-47-exposed mutant female mice spent about half as much time interacting with the familiar mouse than their non-mutant littermates. In a long-term memory test of swimming to reach a hidden platform in a cloudy pool, female mice who were both mutant and BDE-47 exposed did not learn to reach the platform faster after fourdays of training. These behavioral changes in social and cognitive learning specifically in the interaction group corresponded to changes in a known epigenetic regulator of DNA methylation in brain, DNA methyltransferase 3a (Dnmt3a).

LaSalle said that the study results are important because better understanding of the epigenetic pathways implicated in social behavior and cognition may lead to improved treatments for autism spectrum disorders.

“While the obvious preventative step is to limit the use and accumulation of PBDEs in our environment, this would likely be a long-term solution,” LaSalle said. “These pollutants are going to be hard to get rid of tomorrow. However, one important preventative that all women could do tomorrow is to start taking prenatal vitamins before becoming pregnant, as these may counteract the toxins in our environment through DNA methylation,” she said.

A study by researchers at UC Davis conducted in 2011 found that women who reported not taking a daily prenatal vitamin immediately before and during the first month of pregnancy were nearly twice as likely to have a child with an autism spectrum disorder as women who did take the supplements — and the associated risk rose to seven times as great when combined with a high-risk genetic make-up.

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Other authors of the research are Rima Woods, Roxanne O. Vallero, Mari Golub, Joanne K. Suarez, Tram Anh Ta, Dag H. Yasui, Lai-Har Chi, Isaac N. Pessah and Robert F. Berman, all of UC Davis, and Paul J. Kostyniak of the Toxicology Research Center, University at Buffalo, the State University of New York.

The research was funded by grants from the National Institutes of Health and the American Recovery and Reinvestment Act, the National Institutes of Environmental Health Sciences/Environmental Protection Agency Center for Children’s Environmental Health, and the U.S. Environmental Protection Agency Science to Achieve Results (STAR) program.

At the UC Davis MIND Institute, world-renowned scientists engage in research to find improved treatments as well as the causes and cures for autism, attention-deficit/hyperactivity disorder, fragile X syndrome, Tourette syndrome and other neurodevelopmental disorders. Advances in neuroscience, molecular biology, genetics, pharmacology and behavioral sciences are making inroads into a better understanding of brain function. The UC Davis MIND Institute draws from these and other disciplines to conduct collaborative, multidisciplinary research. For more information, visit mindinstitute.ucdavis.edu.