By Nermina Lamadema, Postdoctoral Research Associate at King's College London
The issues of child’s health, it was believed rightly or wrongly, lies fairly and squarely with mothers who carry the burden not only of carrying the offspring but also of all the “blame” for any of their child’s health-related shortcomings. If you are to open any ‘serious’ health magazine worth its salt you are likely to find a whole stream of advices to pregnant women from eat more of this but not too much of that, drink this but definitely none of that, exercises but the right kind and all of these are fine and very useful and without a doubt well-intentioned suggestions indeed. The question is … what about dads? Do they get off scot-free?
What is more recent epigenetics research for example relating to the father lifestyle choices and their effects on the health of their future posterity telling us? More specifically is there anything in this research that implies that the ‘sins’ of the father can leave the imprint on the genome of his future offspring? For a long time, it was assumed that the paternal epigenetic marks are erased completely after the fusion of sperm and egg cell but now we know that some paternal DNA methylation likely survives this process. We will now evaluate the most recent studies that hopefully shed some light on this important issue and evaluate to what extent the environmental exposure and the lifestyle choices of the fathers lead to epigenetic transmission of the acquired information. And as always with the epigenetics there are two sides of the coin so there is strong evidence to suggest that there is a lot to thank the dad’s for and that they truly are the epigenetic heroes.
Research Studies the Good and the Bad
First important area we would like to focus our attention towards is the issue of inheritance of alcoholism within families, which is seen as predominantly being passed down from a father to a son. Previous studies show only a small number of gene variants have been connected to the Alcohol Use Disorder and even a smaller number account for inheritance component. So how is the information passed down? An important study from the University of Pittsburgh shows that a father’s excessive drinking behaviour could set up his son for alcohol abuse even before conception. Using animal models researchers have attempted to address a very important question which is whether father’s exposure to alcohol alters expression of the genes he passed down to his children and lo and behold it was shown that alcohol indeed can modify dad’s otherwise normal genes which are passed to his sons, but surprisingly not his daughters. The epigenetic modification of DNA methylation patterns in the genes of germ cells was the main driving mechanism for this transmission. Looking at the epigenetically transmitted effects of the father’s diet scientists at the McGill University, Canada found that deficiency in dietary folate in a father’s diet could increase birth defects of the offspring by altering sperm epigenome. The genes affected were important for development, and involved in chronic diseases such as cancer, diabetes, autism and schizophrenia. There are numerous other studies assessing the effects of dad’s diet on the offspring health as for example the observation that “low amounts of dietary resources during the father’s pre-adolescence was correlated with a lower chance of cardiovascular mortality in his offspring,” suggesting the protective health effects that a father’s diet can afford to their posterity both children and grandchildren. Similar observations were made with the father’s obesity impacting his child’s likelihood for developing diseases like diabetes or experiencing abnormal metabolic regulation through DNA methylation changes being observed at the very specific genes linked to obesity. Consuming excessive amount of dietary supplements and vitamins which provide methyl donor and cofactors necessary for methyl group metabolism can also epigenetically harm the offspring, affecting the children’s memory and learning ability as shown by the researchers at the Federal Institute for Drugs and Medical Devices and the Helmholtz Zentrum Munich.
The effects of maternal stress on the child’s health have been long studied and from epigenetic standpoint a lot has been recently learned from for Quebec Ice Storm of 1998 which plunged more than 3 million Quebecers into frigid darkness without electricity for as long as 45 days. The babies born five months after that event showed distinct changes in their T cells DNA methylation patterns suggesting the effects on the immune system. What effects does paternal stress have on their children has also been assessed as of recently. Animal studies conducted at the University of Zurich, Switzerland show that fathers exposed to a trauma- like form of stress pass on a distinct mark on the microRNAs in the sperm of the male pups. MicroRNAs are pieces of RNA which prevent the production of proteins and play a key role in genetic expression. One particular microRNA that was elevated, MiR-375, which is linked to stress and metabolic regulation. These patterns are then passed down to the offspring who later on express the same depressive behaviours and other negative consequences as their dad. Stressed dads can also pass on to their children a tendency towards increased high blood sugar and diabetes as shown by the researchers at Shanghai Jiao Tong University School of Medicine where epigenetic changes relating to the stress in form of DNA methylation were detected in the sperm and the liver cells of the fathers.
The age of the fathers was another parameter that was investigate to ascertain what epigenetic effects are brought about and transmitted to the children of the older dads. There is evidence suggesting that in mice older fathers may have children with abnormal social interaction disorders. Other studies to investigate the epigenetic connection and the patterns of inheritance between a father and their children include a study on the exposure to toxicants, like smoking and irradiation, leading to detrimental effects on somatic thymus tissue in their progeny.
Studies which show the positive paternal epigenetic influence are also plentiful. For example, fathers who had a healthy body mass index (BMI) prior to their child’s conception had children with epigenetically unaffected gene for insulin-type growth factor 2 (IGF2), which is a regulator of normal growth and development compared to fathers who overate and were obese.
Studies, such as these, point towards the necessity to consider the effects of both parents’ lifestyles and perhaps help to prepare clinically applicable recommendations for the lifestyle alternations which both parents should consider for the health of their children.
Članak „Epigenetski efekti očevih životnih iskustava na zdravlje djeteta“ na bosanskom jeziku možete pročitati u 21. broju magazina AŠK, jun 2018.