2017/06/24

The Paternal Epigenome Makes Its Mark

Father's lifestyle affects his child's epigenome

https://skinner.wsu.edu/documents/2017/05/5_2017_jama_pressarticle.pdf

Excerpt: "Researchers now understand that sperm contains a memory of a male’s life experiences, ranging from his nutritional status to his exposure to toxic chemicals, said Michael Skinner, PhD, a professor in the school of biological sciences at Washington State University. This information is captured in alterations to the epigenome, the suite ofmolecular on-off switches that regulate gene expression.

Epigenetic information can be embedded in sperm in the form of changes in DNA methylation—the addition of chemical “tags” that switch genes “on” or “off”—or histone modifications—chemical tags on histone proteins, which regulate how DNA is condensed. In addition to these epigenetic marks, researchers also have become increasingly interested in changes in noncoding RNAs, such as microRNAs (miRNAs), which are involved in gene silencing and can be present in sperm.

Last year, a review of human and animal research suggested that epigenetic changes may be the underlying mechanism by which paternal factors such as age, diet, weight, stress, and alcohol consumption contribute to a range of health outcomes in offspring including birth defects, behavioral problems, developmental disorders, obesity, diabetes, cardiovascular disease, and cancer.

A series of studies of historic cohorts from Överkalix in northern Sweden published last decade suggested that information about life experiences could be passed down several generations through the male line and could influence descendants’ health. In 2001 Lars Olov Bygren and coinvestigators from Umeå University in Sweden demonstrated that men born in 1905 who experienced food scarcity before puberty—when primordial sperm cells are developing into mature sperm—had paternal grandchildren with a lower relative risk of early death. The reverse was true for men who had plenty to eat: Their sons’ children were more likely to die young. 
 
...When the collaboration began, Pembrey was director of genetics on the landmark Avon Longitudinal Study of Parents and Children (ALSPAC) at the University of Bristol. In the 2006 article, he and his coauthors also presented data from a cohort of fathers in the ALSPAC study. In this group, men who took up smoking before puberty had 9-year-old sons with higher BMIs than men who first lit up later in life, suggesting that the timing of the ancestral exposure matters. A follow-up study published in 2014 found that the sons of early smokers—who themselves were not necessarily overweight—had an average of 5 to 10 kg more body fat in their teens than their peers.

Several other epidemiological associations between a father’s health prior to conceiving and the health of his children have emerged. For example, there are also some indications that a father’s drinking may contribute to fetal alcohol syndrome– like symptoms, specifically low birth weight, congenital heart defects, and mild cognitive impairments.

Early this decade, a spate of animal studies demonstrated that, in addition to toxins and alcohol, paternal weight and eating patterns—such as high-fat or lowprotein diets—also appear to alter the sperm epigenome and offspring health. In one mouse study, a paternal diet low in folate was associated with an increase in birth defects in offspring compared with a paternal diet sufficient in folate. The fathers who consumed less folate had abnormal methylation of genes implicated in development and chronic disease such as diabetes and cancer.

Studies published last year also suggest a link between paternaldietary patterns or diet-induced weight gain and increased birth weight and breast cancer risk in female offspring.One of these studies identified shared epigenetic changes present in both the sperm of overweightmalemice and the breast tissue of their female offspring. These alterations included reduced expression of miRNAs that regulate insulin receptor signaling, among several other wellcharacterized signaling pathways known to play a role in tumorigenesis. Alterations in miRNA expression may therefore underlie the metabolic reprogramming that, in turn, increases breast cancer risk.

Researchers are just beginning to tease out these underlying epigenetic mechanisms in humans. Investigators on the Newborn Epigenetics Study (NEST) at Duke University provided the first molecular evidence in 2013 and 2015 that a man’s lifestyle may be imprinted on his child’s epigenome.

Soubry suggested that physicians can encourage male patients who plan on conceiving to eat a nutritious diet, quit smoking (even temporarily), drink moderately, and manage stress—all of which the Centers for Disease Control and Prevention already recommends for fathers-to-be. “That advice cannot harm, and I think it can even help to reduce the risks later on for the child,” Soubry said. Of course, behavior matters during pregnancy, too. Fathers—along with mothers and domestic partners—can have a profound effect on the health of pregnancies."

My comment: Abnormal methylation profiles of genes and histones result from poor nutrition, lack of exercise, smoking, alcohol consumption, toxicants and even negative thoughts. Epigenome is your molecular memory and there are several mechanisms in the cell that makes epigenetic memories inheritable. The most stable epigenetic markings are maintained by histone methylation/acetylation and by piRNA-mediated epigenetic silencing. Modern science is aware of lifestyle driven 
epigenetic changes that are the underlying mechanism by which paternal factors such as age, diet, weight, stress, and alcohol consumption contribute to a range of health outcomes in offspring including birth defects, behavioral problems, developmental disorders, obesity, diabetes, cardiovascular disease, and cancer.

Life is not driven by gene sequences. Genes are driven by lifestyle. Don't get lost.