Child Abuse and Trauma "Scars" May Be Passed On To Offspring!

"Child abuse may leave molecular “scars” on the DNA of male survivors, suggesting that health problems related to trauma could conceivably be passed on to future generations, according to a new study led by Harvard T.H. Chan School of Public Health. " Read article...

Can DNA ‘scars’ from child abuse affect future generations? Harvard School of Health. 2018.

A Common Insectide Causes Epigenetic Gene Changes in Offspring Can Lead To Disease Later In Life!

Environmental toxicants have different toxicities and effect the body differently. For this reason, it is important to study them individually to see how each will effect the body upon exposure. Deltamethrin, a synthetic insecticidal pyrethroid, is similar to the pyrethrins which are produced from the flowers of the genus Chrysanthemum. Deltamethrin is a class 2 pyrethroid which means that it is less susceptible to degradation by air and sunlight than those pyrethroids in class 1 and because of this, it is uniquely suited for agriculture. Unfortunately, class 2 pyrethroids are also more toxic to mammals than those in class 1. (1)

While more toxic than its counterparts in class 1, the pyrethroids like Deltamethrin are less toxic than organophosphates that are becoming more and more restricted for use. These restrictions have led to the increase of the use of this pyrethroids and ones like it for everyday use in the US and around the world. The lowered toxicity level is assumed to be because these chemicals are more easily detoxified by mammalian detoxification systems. However, mammalian detoxification systems are not fully developed in young animals and the effects of this chemical on the young was unknown before the conclusion of a study published in 2013. What had been observed before that time was that pyrethroid metabolites, including deltamethrin had been found in the urine of pregnant women and children.

During this 2013 study, pregnant mice were exposed to different levels, 0,1 and 3 mg/kg, of deltamethrin orally every 3 days during gestation and lactation. The purpose was to determine the effects of the pyrethroid on the development of the offspring. As the author describes, "adipose tissue is metabolically active and necessary for systemic energy balance. Adipogenesis requires a number of transcription factors which regulate their development. (2) Until recently, the Nrf2 pathway was thought only to activate antioxidant genes but it been determined that it has a number of other functions, including participating in adipogenesis. (3)  Deltamethrin can be "detected in adipose tissue with a half-life of 5-6 days and is "persistent" in body fat of animal models." (2)

This study was the first to demonstrate that deltamethrin effects adipogenesis and lipid homeostasis at the transcription level in young mice and decrease the expression of some genes at low levels. Previous studies have shown that deltamethrin prevents weight gain with short-term exposure in a non-dose-dependent manner. These observations are consistent with this study's observations of decreased gene expression of adipogenesis. Also, there was a reduction in cytokines levels that may negatively influence the  immune response and interaction with adipocytes. In addition, they found that gene expression of glucose transporters was reduced which consequently may alter glucose transport between tissues and result in an increased risk for obesity, diabetes and glucose intolerance. Thus, deltamethrin may affect normal responses to high fat diets or pharmacological interventions to promote adipogenesis to improve insulin resistance.  Lastly, the researcher determined that many of the reductions in gene expression were due to the epigenetic downregulation by Nrf2 which could lead to alterations in responses to environmental toxicants like endocrine disruptors or obesogens or to changes in diet. (2)

As one can see that while effect of deltamethrin may not be as toxic as those by organophosphates, the impact of exposures to animals, including humans, during development or early in life may be life long. It is also important to be aware that the effects of exposures may not be overtly apparent at first but may be physiologically present through adulthood through epigenetic changes. Epigenetic changes may be permanent and lead to disease development or influence how a person reacts and detoxifies environmental toxicants later in life.




1. Wipedia.

2. Effects of developmental deltamethrin exposure on white adipose tissue gene expression. Journal of biochemical and molecular toxicology, Vol. 27, No. 2. (February 2013), pp. 165-171 by Laura E. Armstrong, Maureen V. Driscoll, Ajay C. Donepudi, et al.

3. Emerging role of Nrf2 in adipocytes and adipose biology. Advances in nutrition (Bethesda, Md.), Vol. 4, No. 1. (01 January 2013), pp. 62-66, doi:10.3945/an.112.003103 by Kevin S. Schneider, Jefferson Y. Chan

Browse the American MedicalID Website!

Effects of Environmental Toxicants are Handed Down to Future Generations!

"A Washington State University researcher has demonstrated that a variety of environmental toxicants can have negative effects on not just an exposed animal but the next three generations of its offspring." Read more....

Washington State University. "Effects of environmental toxicants reach down through generations." ScienceDaily. ScienceDaily, 2 March 2012. <www.sciencedaily.com/releases/2012/03/120302101821.htm>.

Mold Toxin Causes Oxidative Stress, Inhibits Nrf2 and Regulates Autism Genes!

Ochratoxin A is a mycotoxin produced from Aspergillus and Penicillium species. It is commonly found in contaminated food products, water damaged buildings and heating ducts. Currently, it is one of 20 mycotoxins that is monitored in food. Ochratoxin A is known to be nephrotoxic, immunotoxic, and carcinogenic. Therefore, it is a health concern in both humans and animals. 

Generally, Ochratoxin A has been found to induce oxidative stress, inflammation and psychiatric conditions. In males, it is especially neurotoxic. Genes that it upregulates have an effect on autism-regulated genes that decrease Nrf2 and cause high levels of reactive species and oxidative damage.  Research has shown that males are more commonly effected because the genes are found on the x chromosome. 

Mezzelani A. (2017) Ochratoxin A and Epigenetics. In: Patel V., Preedy V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham

Nrf2 deficiency exacerbates ochratoxin A-induced toxicity in vitro and in vivo. Toxicology, Vol. 389 (15 August 2017), pp. 42-52 by Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, et al. www.citeulike.org/user/kimberlykramer2015/article/14620230

Detection of mycotoxins in patients with chronic fatigue syndrome. Toxins, Vol. 5, No. 4. (11 April 2013), pp. 605-617 by Joseph H. Brewer, Jack D. Thrasher, David C. Straus, Roberta A. Madison, Dennis Hooper

A review of the diagnosis and treatment of Ochratoxin A inhalational exposure associated with human illness and kidney disease including focal segmental glomerulosclerosis. Journal of environmental and public health, Vol. 2012 (2012), doi:10.1155/2012/835059 by Janette H. Hope, Bradley E. Hope

Methylation Patterns are Different in Patients With Chronic Fatigue Syndrome!

Methylation is a biochemical process that changes or modifies gene expression without changing the DNA sequences. A recent study has demonstrated that patients with CFS had different methylation patterns than those study participants without CFS. The results seem to confirm past studies that also showed methylation may be a factor in CFS. More research is warranted to find out whether changes in methylation, especially in those genes related to immune response, is caused by CFS or CFS causes changes in methylation patterns. In addition, the author points out that "epigenetic mediation of the connection between genotype and phenotype has recently been proposed and these relationships may be worth investigating in assessments of disease and disease risk."(1) In a subsequent study, they found that "dysregulation in ME/CFS varied depending on the location relative to CpG islands. " (3) 

1. DNA methylation modifications associated with chronic fatigue syndrome. PloS one, Vol. 9, No. 8. (2014) by Wilfred C. de Vega, Suzanne D. Vernon, Patrick O. McGowan. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128721/


2. Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PloS one, Vol. 13, No. 7. (2018) by Malav S. Trivedi, Elisa Oltra, Leonor Sarria, et al.http://journals.plos.org/plosone/article?
id=10.1371/journal.pone.0201066

3. Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). BMC medical genomics, Vol. 10, No. 1. (23 February 2017) by Wilfred C. de Vega, Santiago Herrera, Suzanne D. Vernon, Patrick O. McGowan https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324230/

Epigentics Changes Suspected in Increased Risk for Mental Illness in Those Living in Poverty!

Children from impoverished families are more prone to mental illness, and alterations in DNA structure could be to blame, according to a study published on 24 May in Molecular Psychiatry^1.

Poverty linked to epigenetic changes and mental illness. Sara Reardon. Nature. May 24, 2016. http://www.nature.com/news/poverty-linked-to-epigenetic-changes-and-mental-illness-1.19972

Epigenetics: How Life Memories Are Passed On?

 

According to epigenetics -- the study of inheritable changes in gene expression not directly coded in our DNA -- our life experiences may be passed on to our children and our children's children. Studies on survivors of traumatic events have suggested that exposure to stress may indeed have lasting effects on subsequent generations. But how exactly are these genetic "memories" passed on?

 American Friends of Tel Aviv University. (2016, March 28). Biological mechanism passes on long-term epigenetic 'memories': Researchers discover the on/off button for inheriting responses to environmental changes. ScienceDaily. Retrieved March 29, 2016 from www.sciencedaily.com/releases/2016/03/160328133534.htm

Health Consequences Can Be More Severe When Multiple Environmental Toxicant Exposures Occur at the Same Time!

 

     When people are exposed to environmental toxicants, heath experts can not always predict the level of biological response. In other blogs, I discuss this and attribute it to the fact that every exposure is different in scope and intensity. In addition, every individual will react differently for a variety of reasons that include other environmental factors, overall health status and genetics. This is also true of multiple exposures at the same time or close together in time. With this in mind, scientists and health professionals must assess levels of all exposure to determine health consequences. Unfortunately, the health impacts of multiple exposures can be greater than the health impacts of exposures alone.  Beier et al has demonstrated this to be the case in their new study.
      Other studies have shown that "lead exposure and obesity are co-occurring risk factors for decreased bone mass, especially in low socioeconomic communities. In the Beier study, mice were exposed to a high-fat or low-fat diet. In addition, the mice were exposed to a lifetime of lead (Pb) in their drinking water. The results of the study showed the high-fat diet mice had increased body mass and glucose intolerance. Both the high-fat and lead increased fasting glucose and leptin. Both Pb and high-fat had reduced bone quality and the PB and high-fat together had a worse effect on thesame parameter. Mechanical bone properties of strength were depressed in Pb-exposed bone but was unaffected by a high-fat diet. Both agents promoted osteoclastogenesis and adipogenesis and decreased osteoblostogenesis. Combining Pb and fatty acids combined enhanced the effects of PPAR-y and  inhibited B-catenin.  The author noted that when studying toxicants, 'one must assess them together with other risk factors relevant to human health.'"
      Taking this into account, let us review another study that I mentioned earlier. In that study, it was shown that increased hypermethylation and a decrease in the expression of IFN-Y and regulator T cells occurred when the two toxicants, second-hand smoke and ambient air pollution,were combined. Generally, the decrease on the expression of the T cells and IFN-y was less severe when the exposures happened alone.


Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice. Environmental health perspectives (10 April 2015) by Eric E. Beier, Jason A. Inzana, Tzong-Jen J. Sheu, et al. http://www.citeulike.org/user/kimberlykramer2015/article/13580466

Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical epigenetics, Vol. 4, No. 1. (2012), doi:10.1186/1868-7083-4-17 by Arunima Kohli, Marco A. Garcia, Rachel L. Miller, et al.  http://www.citeulike.org/user/kimberlykramer2015/article/13578755

Gender May Not Be Written In Stone At Birth!

"It was thought that once established, sexual differentiation could not be undone," Nugent told PBS. "Our work shows that sex differences in brain and behaviour are epigenetically regulated, meaning that sex differences are not hardwired in our DNA but programmed during development."

A recent study has shown that gender may be "plastic" and can be changed during development. In the study, researcher showed that neurological sex is more "flexible" than once thought and for the first time they have been able to "flip" the sex of newborn rats causing females to act like males.  The changes suggests that gender within a few days of birth is not "set in stone" as once was thought. This "flipping" is the consequence of epigenetic processes that do not change the sequences of DNA but silences some of the genes and therefore, influences gene function. One might assume that these epigenetic processes can last for a number of years or a lifetime. In addition, the researchers found that not only was their a change in behavior but also a corresponding change in brain structure. 


For further reading:  You and Your Offspring are What You Eat and Pollutants You're Exposed too!



Brain ‘gender’ is more fluid than originally thought, research reveals Science Alert (9 April 2015) by Fiona MacDonald. http://www.sciencealert.com/brain-gender-is-more-fluid-than-originally-thought-research-reveals

You and Your Offspring are What You Eat and Pollutants You're Exposed too!

    

   
     It has been suggested that scientists should look at a decrease in regulatory T cells (Tregs) in environmental diseases. It is suspected that environmental factors may contribute to "noncommunicative diseases like asthma, cardiovascular disease, inflammatory bowel disease and allergic diseases".  He further explains that environmental factors such as nutritional state and tobacco use in utero shapes function, metabolism and body structures which effects offspring and contributes to the development of these types of disease later in life. More studies are needed to see how environmental factors alter the fetal immune responses from these epigenetic changes later in life.
     It is believed that environmental factors like nutrition and pollution shape the microbiome that can lead to allergies. One of the major culprits may be the Western diet. The typical Western diet is lacking in fruits and vegetables and an imbalance of good and bad fats. The author notes this imbalance influences the development of allergies because of the anti-inflammatory nature of Omega 3 fats verses the pro-inflammatory omega 6 fats. He says further, that "there is a decrease in antioxidants that leads to wheeze and lower lung function. In addition, the effect of nutrition on allergies are mediated through immunomodulation, oxidative stress and can be epigenetically controlled.  The more pro-inflammatory the diet and more prevalent the pollutants, the more there are changes to the microbiome and functions of the gut (Yang) and the more numerous the changes to the immune system.( Byoung-Ju)
    In recent years, more studies have focused on the decreased expression of Fox3p Tregs in non-communicable diseases through methylation. Kohli et al. describes how there is a decrease of Tregs from exposure to second hand smoke and ambient air pollution and its consequences were more severe when the individual was exposed to both at the same time. Also,  it showed that many of the effects of these pollutants on Tregs was epigenetically controlled and passed on to offspring if the mother's was exposed to these pollutants while pregnant.  




For further reading: Chemical Sensitivity and Th2 Autoimmune Disease: The Loss of Treg Cells As Referee! http://heirsresearch.blogspot.com/2010/06/commensal-bacteria-induce-tolerance-via.html



Regulatory T cells (Tregs) monitoring in environmental diseases. Collegium antropologicum, Vol. 33, No. 3. (September 2009), pp. 743-746 by Vladimir Mićović, Bozo Vojniković, Aleksandar Bulog, et al. http://www.citeulike.org/user/kimberlykramer2015/article/6090770
Environmental changes, microbiota, and allergic diseases. Allergy, asthma & immunology research, Vol. 6, No. 5. (September 2014), pp. 389-400, doi:10.4168/aair.2014.6.5.389 by Byoung-Ju J. Kim, So-Yeon Y. Lee, Hyo-Bin B. Kim, Eun Lee, Soo-Jong J. Hong. http://www.citeulike.org/user/kimberlykramer2015/article/13578723

Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical epigenetics, Vol. 4, No. 1. (2012), doi:10.1186/1868-7083-4-17 by Arunima Kohli, Marco A. Garcia, Rachel L. Miller, et al. http://www.citeulike.org/user/kimberlykramer2015/article/13578755

[Interactions between the monogastric animal gut microbiota and the intestinal immune function--a review]. Wei sheng wu xue bao = Acta microbiologica Sinica, Vol. 54, No. 5. (4 May 2014), pp. 480-486 by Lina Yang, Gaorui Bian, Weiyun Zhu http://www.citeulike.org/user/kimberlykramer2015/article/13578764