Listen Up Dads! Paternal Weight and Obesity Influences Sperm Epigenetics
The obesity epidemic is a widely discussed, but controversial topic. Although diet and exercise are the best way to combat weight gain, some people seem to gain weight easier than others and have a more difficult time getting rid of it. The role of maternal and prenatal nutrition is concretely linked to offspring metabolic health. However, evidence also suggests that paternal factors contribute to the inheritance of obesity and obesity-related traits, and that children of obese fathers are born with a higher risk of developing metabolic disease later in life, independent of the body weight of their mother.1 A recent paper by Donkin et al. investigates the impact of paternal body weight on sperm maturation and shows that weight loss is able to remodel the epigenetic signature of spermatozoa in obese men.
The group first looked at epigenetic patterns of spermatozoa in obese, glucose intolerant men compared to lean, normal-glucose tolerant men. They tackled the epigenome from three different directions: they used 1) MNase-seq to look at nucleosome positioning and chromatin landscape, 2) sncRNA-seq to evaluate the expression of small, regulatory RNAs, and 3) RRBS to investigate DNA methylation in pure, motile spermatozoal fractions.
First, they found that in obese versus lean men, spermatozoal nucleosome positioning is not altered, suggesting that post-translational modifications of chromatin-organizing proteins such as histones and protamines may not play a large role in passing on traits related to obesity. However specific miRNAs, piRNAs, tRFs, and snRNAs showed altered expression between obese and lean men. Lastly and most significantly, they found 9,081 genes with altered DNA methylation status in spermatozoa from obese men. Of these differentially methylated genes, those related to regulation of CNS development and functions were over-represented, suggesting that children born to obese fathers may have altered brain development and phenotypes. Additionally, the change observed in sperm DNA methylation is consistent with other studies showing association between paternal obesity and altered DNA methylation of imprinted genes in the cord blood cells of offspring.2
To investigate whether these obese-related methylation changes are reversible through weigh loss, the team next compared sperm from morbidly obese men before and after bariatric surgery. Sperm samples were collected one week before surgery, one week after, and one year after surgery once weight loss had stabilized. Comparisons identified differential methylation in 1,509 unique genes 1 week after surgery and in 3,910 genes after 1 year, suggesting that weight loss is able to induce changes in the sperm epigenome. Although sperm takes 3 months to mature, significant changes in the epigenome were observed after only one week. The authors hypothesize that this suggests that DNA methylation patterns are solidified during the last stages of sperm maturation.
Donkin et al. shows for the first time that obesity in men leaves a distinguishable epigenetic signature on their sperm that is capable of being passed on to their children. Possibly more significant, they also show that obesity-related changes in sperm DNA methylation can be reversed by weight loss, adding to growing evidence that paternal health and diet is equally important as maternal lifestyle for offspring health and development.
Donkin, I., Versteyhe, S., Ingerslev, L., Qian, K., Mechta, M., Nordkap, L., Mortensen, B., Appel, E., Jørgensen, N., Kristiansen, V., Hansen, T., Workman, C., Zierath, J., & Barrès, R. (2015). Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans Cell Metabolism DOI: 10.1016/j.cmet.2015.11.004
1. Lake, J., Power, C., & Cole, T. (1997). Child to adult body mass index in the 1958 British birth cohort: associations with parental obesity Archives of Disease in Childhood, 77 (5), 376-380 DOI: 10.1136/adc.77.5.376
2. Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, Kurtzberg J, Murtha A, Jirtle RL, Schildkraut JM, & Hoyo C (2015). Newborns of obese parents have altered DNA methylation patterns at imprinted genes. International journal of obesity (2005), 39 (4), 650-7 PMID: 24158121