July 9, 2018

(working title)

Epigenetics and pregnancy.

Humans, like most organisms on earth, grow and maintain their biological systems through a complex interplay between the environment and their genes. Epigenetics is the study of the ability of environmental signals to silence or activate genes, thus effecting cellular function and species survival. I was once given the analogy that your genes are like a computer hard drive.

They do nothing until the software inputs change activity. The environmental signals like food, chemicals, stress and much more are the putative software inputs for us. Good lifestyle inputs have been epidemiologically proven to reduce disease risk.

Pregnancy is probably the most critical epigenetic period of human life where the development of a child is affected by many aspects of our lifestyle. What we do know is that negative epigenetic triggers will have a negative effect on a child's outcome. We need to know what the negative triggers are.

"As a fertilized egg develops into a baby, dozens of signals received over days, weeks, and months cause incremental changes in gene expression patterns. Epigenetic tags record the cell's experiences on the DNA, helping to stabilize gene expression. Each signal shuts down some genes and activates others as it nudges a cell toward its final fate. Different experiences cause the epigenetic profiles of each cell type to grow increasingly different over time. In the end, hundreds of cell types form, each with a distinct identity and a specialized function." (learn.genetics.utah.edu)

The beginning of this new scientific understanding came in the year 2000 from the lab of Randy Jirtle, a radiation oncologist at Duke University in North Carolina. His pioneering research with the Agouti mouse revolutionized how we see human genetic outcomes and changed our belief that we are destined to be the sum of our parents inherited DNA. They also proved that mother's have some control over their offspring's genetic outcome.

His lab conducted an experiment with an Agouti mouse. This mouse is predestined, or so we thought, to always produce pups that have a yellow coat color, become obese and are prone to developing diabetes and cancer. This elegant experiment offered the mother mouse an altered diet prior to conception and then throughout pregnancy. They gave the mice dietary sources of a specific carbon complex called a methyl group which is naturally found in choline, betaine, folate, and vitamin B12. The natural food sources of these methyl groups are predominantly vegetables like beets and garlic.

What they proved was that this dietary addition had the ability to silence a segment of the offspring's genetic code. This silenced region coded for the Agouti mouse's coat color and predisposition for obesity. The outcome was earth shattering in the scientific world. The mouse pups were born brown and skinny and did not carry the risk of developing diabetes or cancer.

"It was a little eerie and a little scary to see how something as subtle as a nutritional change in the pregnant mother rat could have such a dramatic impact on the gene expression of the baby," Jirtle says. "The results showed how important epigenetic changes could be." (Discover article 2006)

Let me recap! For the first time in human history, we now have evidence that a nutritional alteration has the ability to alter the disease outcome of a new baby. Healthy food is the lifestyle choice that had a positive effect on the outcome in a mouse model that was supposed to not be possible!

Dr. Jirtle's group took the research a little farther. They continued the original agouti mouse experiment, but added a wrinkle. They gave the mothers a ubiquitous plastic chemical called bisphenol A, BPA, at the same time as they continued the original experimental design. The outcome was again shocking. The offspring reverted back to the original dysfunctional state of yellow coat, obesity and increased disease risk.

These studies proved that for the first time we were aware that genes could be activated or turned off by environmental signals including beneficially with food and detrimentally with chemicals.

"Epigenetics is proving we have some responsibility for the integrity of our genome," Jirtle says. "Before, genes predetermined outcomes. Now everything we do-everything we eat or smoke-can affect our gene expression and that of future generations. Epigenetics introduces the concept of free will into our idea of genetics." (Discover article 2006)

Next week: Epigenetic and Szyf's work

Dr. M

 

Utah Genetics Site
M. Szyf Article
Szyf Transcript
Project Ice Storm
M. Kundakovich Article
R. Jirtle Article
D. Dolinoy Article
Discover Article