On September 11, 2001, passenger jets struck the Twin Towers, leveling them, killing thousands of New Yorkers, and traumatizing tens of thousands more. Among those directly affected, but not killed, by the attack were 1700 pregnant women. Some of those women developed post traumatic stress disorder, some did not. When the PTSD-positive group had their kids, their cortisol secretion was lower and stress response to novel stimuli was impaired. Although as fetuses they weren’t conscious of the chaos, it affected them as if they had directly witnessed the blast. The affected children were no different genetically – they didn’t have “the stress gene.” Rather, the activity of the genes that regulate the stress response had been altered by an environmental input.
This was epigenetics in action.
Epigenetics isn’t just relevant to pregnant women and their offspring, either. Dads matter too. In one recent study (PDF), male mice were subjected to ongoing chronic, intense stress. They were placed in cages with and beat up by larger, more dominant males. Essentially, they were bullied for ten days straight. This gave them the mouse versions of PTSD, depression, and severe anxiety. After, they bred with normal females. Their pups were born “stressed out” and anxious, uninterested even in sugar water when subjected to stressors. The anxious pups avoided social contact with other mice as much as possible. The pups’ mothers weren’t exposed to stress during pregnancy; only the dads’ life experiences before conception could explain the differences, which correlated with changes to gene expression in the pups.
Epigenetic shockwaves can reach far into the future, too. Until the 20th century, the people of Overkalix, Sweden were at the mercy of the elements. Winter brought total isolation, with every route into and out of the municipality completely frozen over and inaccessible. That meant if the harvest was poor, the people flirted with starvation. If the harvest was good, they prospered and thrived. It was either famine or feast. In 2002, Swedish researchers analyzed the extensive birth, death, and health records of the area to see how this feast and famine cycle of the 19th century might have affected the health of the population. Amazingly, they found that boys who ate very well during late childhood were more likely to go on to have grandsons with health issues like heart disease, diabetes, and early mortality later in life. On the other hand, boys who experienced famine during late childhood had longer-lived grandsons with fewer health problems.
What does this all mean?
That our choices are bigger than us. It’s easy to see how the foods we eat, the exercises we do (or don’t), and all the other choices we make can affect our own health, in this lifetime. Anyone who’s ever made a positive change to their lifestyle and seen the subsequent health benefits can attest to that. But these stories indicate that those very same life experiences can send epigenetic shockwaves to your offspring – and in some cases your offspring’s offspring. There’s more to it than bullied mice, Swedish famines, and terrorist attacks, though, as you’ll see below. The life experiences of both moms and dads can exert a wide range of powerful effects. But how, exactly?
Maternal Epigenetic Transfer
Moms transfer epigenetic effects via two routes. First, as an epigenetic factor herself. After all, the mom is the primary environment for the fetus. Anything that happens to the mom – famine, stress, overnutrition, undernutrition, chronic sleep loss, terrorist attack – also happens to the fetus, sometimes even if it occurs pre-conception. Second, when a woman is pregnant, she’s not just carrying the fetus and transmitting epigenetic changes to the fetal genes from her life experiences. She also carries the fetus’ reproductive cells which will either develop into eggs or sperm. Any changes to the gene expression of these reproductive cells during their development in the fetus may also affect subsequent offspring. So at least three generations are affected by the environmental input during pregnancy: the mom, the fetus, and the fetus’ future offspring.
Paternal Epigenetic Transfer
Dads transfer epigenetic inheritance through changes to the sperm. If a male fetus is subjected to an epigenetic input in the womb as his reproductive cells are developing, he may grow up with forever altered sperm that in turn affects his progeny. As seen in the case of the Swedish village, male sperm may also be vulnerable in late childhood right before puberty, which is when sperm cells are maturing and “finalizing.” And then you’ve got the mouse studies that suggest inheritance can transfer even when the father’s experiences happen as an adult. The amount of research into paternal epigenetic transfer pales in comparison to that of maternal epigenetics, but it appears to play a role just the same (if perhaps not as prominent).
It’s easy to get bogged down in epigenetic mechanisms, but what you’re really here for is to learn how we can shape our offspring’s health. Let’s explore, shall we?
Nutrition – the types of foods we eat, the numbers of calories we consume, and our overall metabolic state – plays perhaps the biggest and best studied epigenetic role in the health of our offspring. A few examples:
Among isogenic (identical, genetically) mice, those born to obese and diabetic mothers showed changes in liver gene expression that predisposed them to obesity when faced with a Western-style diet. In other words, mice born to leaner mothers weren’t just leaner, they were somewhat epigenetically resistant to the obesogenic effects of the Standard American Diet.
Lesson? Avoid obesity and diabetes during pregnancy (and always, really). You can’t force your kids to eat Primal, but you can set them up for metabolic robustness.
In contrast to the earlier example of grandfathers who spent the formative years of their childhood in lean times siring grandsons with better metabolic health and longevity, mothers who experienced undernutrition during pregnancy gave birth to offspring with altered hypothalamic gene expression, a propensity to overeat, disrupted glucose tolerance, and lowered energy expenditure – the kind of gene expression that would help someone survive starvation. Those same epigenetic changes to gene expression were also found in twin lambs born to both underfed (a period spanning 60 days prior to and 30 days after conception) and well-fed sheep, suggesting that it’s the “perception” of famine (whether actual or imagined) that triggers the starvation epigenome.
Lesson? Don’t try to diet and restrict calories while pregnant. Weight gain is totally normal, healthy, and necessary when building a tiny human inside your body.
Male mice who were fasted for a day or two a few weeks before mating sired offspring (both male and female) with consistently lower blood glucose levels than controls. It isn’t clear whether this is a positive alteration, however, as too low a blood glucose level can hamper growth and development.
Lesson? The occasional skipped meal, or series of meals, doesn’t just affect your health (in a mostly positive way), but the health of your offspring. Whether lower blood glucose is a good or a bad thing is conditional.
Pregnant women are advised to increase their intake of folate and other vitamins to prevent birth defects and make up for a substandard diet. This is generally good advice, but there is such a thing as “too many vitamins.” In one study, pregnant mice fed a high-folate diet (10 times the normal amount) had offspring with an epigenetically enhanced propensity for obesity unless they were weaned on a similarly high-folate diet. Another study found similar obesogenic epigenetic changes in male offspring of rats taking ten times the normal amount of a multivitamin.
Lesson? Get most of your nutrients from food whenever possible, and don’t overdo the prenatals (also, make sure you take folate, not folic acid).
In pregnant mice on an imbalanced diet (wildly variant ratios of folic acid and B vitamins), maternal omega-3 intake ameliorated some of the negative epigenetic effects normally caused by the nutrient imbalance.
Lesson? Get your omega-3s.
Even the source of maternal dietary protein during gestation seems to affect gene expression in the offspring. In pregnant mice given soy as a protein source, offspring were fatter and had elevated insulin when compared to offspring from casein-fed mice, an effect mediated by an increase in gene expression in the area of the brain that controls food intake.
Lesson? Skip the soy protein shakes.
Some pregnant women are advised to restrict dietary protein. In animal studies, this appears to have negative epigenetic effects on the fetus, including the “programming of hypertension.”
Lesson? Eat protein to satiety when pregnant.
Maternal choline affects the expression of cortisol regulation in the fetus. This likely explains why mothers with a high intake of choline during pregnancy have kids who appear to be protected against stress-related disorders through epigenetic factors.
Lesson? Eat your liver and egg yolks.
Maternal (and paternal) stress is one of the largest area of study in epigenetics, probably the largest besides nutrition.
Using a mouse model of prenatal stress, researchers were able to epigenetically trigger neurological and psychiatric disease states in the offspring. Prenatal stress induced microRNA regulation at sites in the fetus that affect and/or induce multiple sclerosis, schizophrenia, brain inflammation, and bipolar affective disorder.
Lesson? It’s not like a traffic jam in the 2nd trimester is going to give your kid schizophrenia, but it does illustrate the worst-case scenarios associated with prenatal stress.
Even the mom’s mood during pregnancy exerts an epigenetic influence on the outcome of the pregnancy. If a mom was depressed or anxious during the 3rd trimester, her offspring was more likely to have altered cortisol regulation, including increased cortisol responses to stress at three months.
Lesson? Relax, kick your feet up, and try not to let daily stressors consume you during pregnancy. Easier said than done, I know. Also, don’t let the stuff from the previous section – what you’re eating – turn you into a ball of stress. Eating anything can be hard when you’re pregnant. Just make the best choices you can, and make your “bad” choices better.
Six weeks of chronic stress were enough to alter the microRNA (a regulator of gene expression) of sperm in male mice, whether the stress occurred in adulthood or childhood. When those mice later bred, they sired pups with dysfunctional stress responses reminiscent of neuropsychiatric disease. Another stressed out mouse dad study had similar results: altered stress responses in the offspring.
Lesson? Stress matters for dads, their sperm, and their offspring, too. Not just the moms are vulnerable.
Research into the prenatal or preconceptional epigenetic effects of other lifestyle factors is limited, but we can still make some predictions. Let’s take a look.
Exercise – One recent study found that exercise can affect the quality of sperm and upregulate gene expression across generations. Both maternal and paternal exercise, for example, improve memory and spatial learning in the offspring (paternal exercise only seems to benefit male offspring, but dads should probably still work out just to be on the safe side). A word of caution: though exercise is generally “a good thing” for your offspring, remember how vulnerable the fetus is to maternal stress. Don’t do too much!
Sleep - We know that melatonin (the “sleep hormone”) is an important player in “fetal programming,” and a recent study found that rats who were sleep deprived during gestation produced offspring with reduced antioxidant activities and/or altered homocysteine levels, so sleep clearly plays an important role in fetal epigenetics.
Sun - While there’s nothing that explicitly looks at the effect of sunlight exposure on fetal development, there are links between maternal vitamin D levels – a fair proxy for sunlight – and epigenetic regulation of fetal bone development and osteoporosis later in life.
Dirt – “Maternal exposure to animal sheds” and other farm environments during pregnancy might actually make the offspring more resistant to allergies right out of the womb.
Much of this is still up in the air, of course. We haven’t identified every lifestyle factor that triggers epigenetic changes in offspring, nor will we (likely) ever. But most of the evidence that we do have suggests that being healthy is good for our offspring and being unhealthy is bad for them. So, being an obese dad or mom? Not so good for the kids and grandkids. Being a healthy weight mom or dad? Probably good for the kids and grandkids. Smoking during pregnancy? Bad. Going for nature walks during pregnancy? Probably good. Getting a good 8-10 hours of sleep while pregnant? Good. Staying up late watching bad TV with a kid in your belly? Not so great, most likely. Playing? Good. Even if there isn’t a study for everything, it’s already been shown that most lifestyle modifications affect us on the epigenetic level. I don’t think it’s a stretch to assume that they’re also affecting our children on the epigenetic level.
Some of you may find this a bit scary. You may even feel helpless, as if decisions were made concerning your longterm health before you were born, or even before your parents were born. For my money? It’s the opposite. It’s empowering, because knowledge truly is power, and now you have the power to not just transform your own health, but also the health of your unborn progeny’s progeny. That may sound like a lot of responsibility – and it is – but it’s not anything you aren’t already doing for yourself. Just stick to what you know works, eat right, stay active, avoid unnecessary stress, get plenty of sleep, get away from the city now and again, laugh everyday, give and get massages, walk a lot, lift heavy things, eat lots of plants and animals, and all that epigenetic stuff will take care of itself.
Most importantly, remember that you have just as much power to create lasting health benefits in your children with the choices you make. It’s not just about avoiding unhealthy outcomes, but creating healthy ones!
Anyway, that’s it for today. It was a long but important one; thanks for sticking around. Leave your thoughts, questions, concerns in the comment section, as well as any other bits of evidence you’ve found that shows how we can affect our offspring.