Paternal Epigenetics, Fetal Development and Lifestyle Factors (Oh my!)

Welcome to “This Week in Parenting Research”, an (allegedly) twice a month column where we discuss new research that may be of interest to parents or anyone who spends a lot of time around kids.

This week, I ran across a really interesting paper called “Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype“. Sounds kinda dry, I know, but it was REALLY interesting. Not convinced? Let me start at the beginning.

First off, what does epigenetics mean and why did they care?

The dictionary definition of epigenetics is “the study of the way in which the expression of heritable traits is modified by environmental influences or other mechanisms without achange to the DNA sequence.” There’s a lot to this field, and a lot of work has gone in to getting a precise definition, but for the purposes of this paper it basically ended up meaning “things about Dad that were true at the time of conception that could affect the baby”. Historically of course, research of that type has focused on mothers because it seemed so obvious that the one carrying the baby could affect it’s development. Recently however it’s been hypothesized that certain paternal “preconception exposures” could actually affect development as well. This paper wanted review the literature around paternal exposures and see what the current evidence was. 

Okay, so what type of things were they looking for?

Well, to reiterate, this is a really new field. The authors basically were looking for ANY paper that suggested a paternal influence. They ended up with lots of epidemiological and animal studies, which are both good for laying groundwork but NOT sufficient to prove causation in humans. A few areas they looked at:

1. Paternal Age
2. Paternal Malnutrition/chronic lack of food
3. Paternal Obesity
4. Paternal Smoking
5. Paternal Radiation exposure
6. Paternal Psychosocial stress
7. Paternal Alcohol consumption

These things seemed reasonable, since all of those things are quite common to warn those who are pregnant/looking to become pregnant about.

Any caveats before we get going?

It should be noted that two of the hardest things to control for doing this type of research are 1) maternal factors 2) regular genetics. In order to prove something comes from one parent or the other, you’d have to find a discordant pair….ie a mother who never suffered from malnutrition but a father who did. Since conditions like famines often effect whole regions, it’s very likely both parents will have been exposed.

For other issues, it can be hard to separate epigenetics from plain old genetic inheritance. Obesity is a good example of something we know can be genetic, so differentiating that from an epigenetic cause could be difficult.

Alright, so what did they find?

Let’s break it down by category:

Paternal age: Quite a few epidemiological studies have been done on this, and it does appear those of “advanced paternal age at conception” (normally defined as over 40 or 45) are more likely to have children with schizophrenia, autism, birth defects and Down’s syndrome. A mechanism for this has been proposed, but not established so causation isn’t proven. It’s not clear if these papers controlled for maternal age as well.

Paternal malnutrition/chronic lack of food: There has been one Swedish cohort study that suggested a lack of food during paternal adolescence could affect the health of future children. Oddly, it actually helped by LOWERING the risk of cardiovascular mortality. Additionally, there have been some studies in mice that showed changes in glucose levels for the offspring of fathers who were denied food.

Paternal obesity: The studies here actually only looked at the hypomethylation of certain genes (a classic epigenetic modification). They showed that obese men tended to have hypomethylation of genes related to obesity, and that their children did as well.

Paternal smoking: Smoking has been shown to result in damaged DNA in ejaculated sperm, but there are no studies addressing how this may affect children.

Paternal radiation exposure: Unsurprisingly, mouse studies have shown that paternal radiation exposure actually results in quite a few consequences for the offspring. It decreases the overall viability of the children, and affects the thymus tissue. Consistent clinical consequences have not been documented in humans (but maybe just avoid this one outright anyway).

Psychosocial stress: This one only has a mouse study, but the findings were intriguing. When male mice were exposed to a repeated stressor, their subsequent offspring didn’t react as strongly to the same stressor as other mice. No human studies, but an intriguing hypothesis.

Paternal alcohol consumption: I was interested to read that 75% of children born with Fetal Alcohol Syndrome actually have fathers who are alcoholics. While fetal alcohol syndrome/alcohol warnings are almost always aimed at women, it’s interesting that chronic paternal alcohol consumption can cause hypomethalation of genes even if the mother drinks no alcohol at all. While there are not many human studies on this, mouse studies have shown symptoms in offspring of fathers who were exposed to alcohol. Additionally, human studies have shown an increase in birth defects when the father drinks. Again, causation is not proven, but it’s an interesting start. Here the study authors went a step further than with most of the other studies saying “Overall, these studies imply that early changes in a father’s lifestyle can decrease prevalence of congenital disorders in his offspring.”

So what does this all mean? Well, maybe something, maybe nothing. Epigenetics is still a growing field, and one that can face a lot of challenges. As I stated repeatedly, the studies that have been done have not yet proven causality….they are still in the “establish association and investigate possible mechanisms” phase. At this time there are no specific recommendations for behavior changes, but it’s at least interesting to see what’s being looked at.
As we examine the data though, it’s also important to remember what Prof Allen Pacey said in this article that got some expert reactions to the paper:

 “I think there is a real danger that men (and women) take on too much guilt and burden about their lifestyle when they are trying to start a family. This has the potential to cause significant stresses and strains within the relationship, which in itself is not healthy. I think the best advice to anyone is to try to start a family as early in their lives as possible (modern life permitting) and during the pre-conception period just try and be as healthy as possible. I don’t think men (or couples) should try and start faddy diets or do whacky lifestyle changes. It’s probably a good idea for smokers to try and give up as the chemicals in tobacco or cannabis smoke are quite harmful. But as for everything else, just be sensible and do it in moderation.”

Featured Image Credit: Found here from Enzymlogic