Epigenetics and pregnancy stress: should we be scared?

Preparing for a child is hard, and it’s only exacerbated by all the information that gets thrown at mothers about what to do and what not to do.

One of these common ideas is that if a mother experiences stress when pregnant, her offspring will suffer. But don’t panic – genetics is highly complex biology that isn’t as scary as it sounds.

Researchers have found that long, stressful situations can change a mother’s biology, which in turn can affect offspring. The most famous case was among mothers who were pregnant during the Dutch Hunger Winter of 1944–45. The offspring of these women had higher rates of average obesity, diabetes and schizophrenia.

More recently, a study showed that genetic ‘warnings’ were placed in the eggs of female ringworms when they experienced long periods of stress. If that stressful period was long enough, the warnings were even passed on to grandchildren.

Again, it sounds scary, but what does it all mean?

Epigenetics – telling genes what to do.

Genes hold information to make proteins, which are the molecules in our body that carry out most of the work and contribute to our characteristics. The genes are like blueprints that are accessed when a certain protein is required, and the process is dynamic and changing.

However, there are some factors that change when and how often the gene blueprints are accessed, so that certain proteins are expressed differently. These extra factors act almost like bookmarks along the genome.

Sometimes these bookmarks can be inherited – this is called epigenetics.

These bookmarks are often placed on the genome of a foetus when the mother experiences stress, almost as advice about which genes are useful. Usually, this advice is ‘forgotten’ after one generation, but occasionally it remains.

“Genes have ‘memories’ of past environmental conditions that, in turn, affect their expression even after these conditions have changed,” says Veena Prahlad, a biologist at the University of Iowa. “How this ‘memory’ is established and how it persists past fertilisation, embryogenesis, and after the embryo develops into adults is not clear.

 “This is because during embryogenesis, most organisms typically reset any changes that have been made to genes because of the genes’ past activity.”

What happened with worms

Prahlad and her team wanted to learn more about how this happened. They did so by testing how female ringworms respond to heat stress.

They found that the memory of useful genes when it was hot became ingrained in eggs, even before the egg was fertilised. This happened because a protein – called heat shock transcription factor (HSF1) – became upregulated when it was hot and told certain genes to express proteins that would help the future embryo.

Interestingly, HSF1 also recruited another enzyme that normally erases bookmarked memories from an embryo’s genome. When under stress, the enzyme did something different.

“We found that HSF1 collaborates with the [enzymes] that normally act to ‘reset’ the memory of gene expression during embryogenesis to, instead, establish this stress memory,” says Prahlad.

One of the genes affected encodes for the insulin receptor, changing how often it was switched on.

Normally in humans, insulin receptors are very important in regulating the metabolism. However, this was altered in the worm eggs so that the embryos responded less to insulin and switched over to relying on other responses that may not have been as quick, but also have long-term resilience.

“What we found all the more remarkable was that if the mother was exposed to stress for a short period of time, only progeny that developed from her [egg] cells that were subjected to this stress in utero had this memory,” says Prahlad.

“The progeny of these progeny (the mother’s grandchildren) had lost this memory.

“However, if the mother was subjected to a longer period of stress, the grandchildren generation retained this memory.

“Somehow the ‘dose’ of maternal stress exposure is recorded in the population.”

There is a lot more to be researched about HSF1, but it does raise some interesting questions – is this even bad?

Epigenetics doesn’t have to be bad

It is easy to fall into the doom and gloom surroundings stories of what helps our children the most, but when it comes to genetics and epigenetics, it isn’t something on which to dwell. There is little that can be changed about it, and the effects are often so minute as to be negligible.

Like many things that happen in the body, epigenetics has lots of good effects.

For example, the worms born in the experiment are much more tolerant to heat, and this is very beneficial if they live in a hot environment.

Beyond this, epigenetics is constantly changing – that’s why the mothers’ genes can be regulated differently when under stress than at other times. Just as our own environments are changing, so are our epigenomes, and we might not notice all the good it is doing.

Going back to the Dutch Hunger Winter, the offspring may have had a higher rate of average obesity and diabetes, but we don’t know very much about whether other characteristics, such as resilience and ability to build good fats and muscle, were affected.

Epigenetic factors can pull us through hard times by bookmarking the most useful genes, but they can also be passed on in good times, like when we have access to nutritious food.

In fact, epigenetics is an important field in cancer research, because we may be able to alter the bookmarks to fight back against the disease.

Overall, there is no point trying to alter our epigenomes. It is a fascinating and complex field, but it doesn’t have to be another thing for mothers to worry about.