07 December 2015

Obesity caused epigenetic changes in sperm

Ekaterina Korzeneva, N+1 
Danish scientists from the University of Copenhagen have concluded that obesity causes epigenetic changes in men's sperm. This information can be passed on to their children and increase their likelihood of developing obesity. The data of this study are published in the journal Cell Metabolism (Donkin et al., Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans).
Now there is ample evidence that children born to obese fathers have a high risk of developing this disease in adulthood, regardless of the state of the mother's metabolism. It is known that the key external factors provoking the development of obesity – inactivity and excess calories in food – cause changes in the status of DNA methylation (epigenetic changes) of adipose tissue cells and skeletal muscles. Scientists from the University of Copenhagen have for the first time found out how these changes affect the DNA of sperm cells and, thereby, the inheritance of obesity risks.
To answer this question, the authors of the study collected sperm samples from 23 Europeans at the reproductive age from 20 to 40 years. In this group, 13 patients had a normal constitution and a body mass index (BMI) of 22.9, and 10 patients were obese (BMI 31.8). The pattern of histone location, the expression level of short non-coding RNAs (sncrnas) and the level of DNA methylation were analyzed in all samples. These tests showed that the packaging of genomic DNA in the sperm of obese men does not differ from the packaging of DNA in slim men. This factor is an important indicator of fetal development.
SNCRNAS are a group of different RNA molecules directly responsible for the epigenetic inheritance of traits. In obese patients, the overall level of expression of these molecules was increased compared to healthy men. 
DNA methylation occurs in certain parts of the genome and is important for fetal development, and the DNA methylation profile is inherited by the child on the paternal side. The results of the study revealed that in obese patients, an increased frequency of DNA methylation is observed in the area associated with protamines and responsible for packing DNA in spermatozoa and transmitting genetic information to the fetus. In addition, a statistically significant increase in the methylation profile was found in the DNA of genes responsible for appetite control and the development of the nervous system. 
Scientists have also found out how weight loss affects the epigenome of human spermatozoa. To do this, semen samples were examined from 6 men who underwent bariatric surgery – surgical interventions to reduce weight and risk of type 2 diabetes. Samples were taken 1 week before and after surgery, as well as a year after it, when the patients' weight stabilized. These studies have shown that the DNA methylation profile is able to change rapidly as a result of weight loss. Epigenetic changes most likely occur in the last stages of sperm development and are concentrated in the genes responsible for the metabolism and development of obesity and related signs.
Diagram from an article in Cell Metabolism – VM
The results of the study indicate that in healthy men and obese patients there are a large number of epigenetic differences in all body tissues, including sperm. The latter circumstance is of particular interest, since it can directly lead to functional consequences in children whose fathers are obese.
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07.12.2015

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