Toxins May Affect Epigenetics Through Multiple Generations

toxins epigenetics

Organic foods are rather popular in shopping baskets nowadays. After all, avoiding those pesky pesticides that are used on a vast amount of produce is surely good for our health. But what about the health of our children and their children thereafter?

We already know that the life experiences of our mothers and fathers can influence the epigenetics in their children. Epigenetics may also be ‘remembered’ through the phenomena known as transgenerational inheritance; so the pesticides your great-granddad may have consumed could actually have influenced your epigenetics.

Researchers from Washington State University decided to delve into this mystery, focusing on the notorious – and now banned – pesticide DDT, or dichloro-diphenyl-trichloroethane. The group found that a whole slew of epigenetic modifications change as a result of DDT exposure in mice across three generations. Their study was published in BMC Epigenetics & Chromatin in February of 2018.

To provide a bit of background, epigenetic transgenerational inheritance is the concept that epigenetic modifications can be inherited from generation to generation to generation and so on. There is currently a large debate in the field as to precisely what epigenetic modifications can be inherited and if these pass down to the third generation (F3). The reason why the F3 is focused on is because they are not exposed to any environmental influence of great grandparents (F0), as the embryo (F1) and the embryo’s germs cells (F2) can be exposed.

DDT epigenetics and health
DDT was banned in the US in the 1970s, yet its effects on people’s health continue to be felt decades later.

Michael K. Skinner, PhD, a professor in the School of Biological Sciences at Washington State University looked into this, focusing on a pesticide probably consumed by our great grandparents, DDT. Having already demonstrated that DDT exposure can promote the inheritance of obesity, Skinner and his colleagues looked into this further by analyzing a wide array of epigenetic modifications across the entire genome.

Focusing on the broad changes in epigenetic modifications, Skinner looked at the differential DNA methylation regions (DMRs) and non-coding RNA (ncRNA) to see if such epigenetic marks were altered between mice lineages exposed to DDT and those that were not.

The results show completely different and unique combinations between the generations when compared to control mice, indicating that exposure to DDT can affect the mouse epigenetic signatures.

DNA methylation occurs on cytosine at C:G dinucleotides and has a long track record of being a mark for inactive gene expression and heterochromatin. The role of ncRNAs can vary however, their influence in epigenetic regulation yet to be elucidated as different ncRNAs play varying roles in the expression of genes. For instance, some can turn genes on, some turn genes off.

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DNA methylation and ncRNA are likely to function in tandem with another epigenetic regulator, the location of histones and their modifications. In fact, the most significant finding of this study comes from when Skinner decided to focus on differential histone retention regions (DHRs) – in basic terms – the location of histones.

DHRs didn’t actually vary much between the F1 and F2 DDT lineages when compared to the control, but this spiked to a significant degree in the F3 generation, which didn’t even have direct exposure to DDT. Various DHR sites were also found relative to the histone modification H3K27me3 in the F3 generation, an epigenetic mark previously shown to play a role in transgenerational inheritance.

The results demonstrate a variety of epigenetic marks can be altered due to an environmental toxin, but it is still unclear how these all work to influence transgenerational inheritance.

The researchers explained: “The developmental role of DNA methylation and its ability to respond to environmental stressors, the distal actions of ncRNA to help integrate the other epigenetic marks and alter gene expression, and the ability of sperm histone retention and modifications to alter early development of the zygote and early embryo all may work together to facilitate the epigenetic transgenerational phenomenon.”

Due to the potential impacts on disease etiology and other areas of biology, the research team recommends additional investigation and elucidation of these integrated epigenetic processes. The whole seems to be greater than the sum of its parts, how the whole works together is yet to be elucidated but albeit exciting.

 

Source: Read this study and look at Skinners findings here: Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease. BMC Epigenetics & Chromatin. 2018

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James Cain
About James Cain 1 Article
James Cain has recently graduated from the University of Leeds with a Masters in Biology, his project focused on the epigenetic mark H3K4me3 and its role in regulating genes in the wonderful worm, C. elegans. He has been interested in epigenetic regulation ever since he was first taught its concepts during his undergraduate and is excited to see where the field goes in the future. You'll pleasantly find him playing squash, making focaccia or reading a book during his free time.

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