Editors' ChoiceObesity

Daddy dearest: Obesity alters the sperm epigenome

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Science Translational Medicine  23 Dec 2015:
Vol. 7, Issue 319, pp. 319ec217
DOI: 10.1126/scitranslmed.aad9009

Obesity results from complex interactions between genes, behavior, and the environment. Although the bulk of research on the role of the prenatal environment in the development of obesity is focused on the influence of maternal factors—body mass index, diet, and physical activity—on offspring obesity risk, perhaps mom shouldn’t take all the blame. Data from some animal studies suggest that fathers might pass on the risk for obesity and related diseases through epigenetic mechanisms—heritable modifications in the expression of genes without changes in underlying DNA sequences.

Here, Donkin et al. investigated epigenetic changes in human sperm related to paternal obesity. The team observed marked epigenetic differences between the sperm of 13 lean, glucose-tolerant men and 10 obese, insulin-resistant men, including differences in small noncoding RNA expression and DNA methylation patterns of over 9000 genes. To examine the effects of weight loss on the sperm epigenome, the group compared DNA methylation patterns in sperm of six morbidly obese men before bariatric surgery, 1 week after surgery, and 1 year later. They saw changes in 1500 genes after one week and over 3900 genes after one year, with many of the genes being the same as those identified in the cross-sectional study comparing lean and obese men. These genes included several known regulators of appetite, as well as genes previously shown to correlate with obesity.

Additional work will determine if the epigenetic changes observed in sperm affect the metabolism or obesity risk in future children. However, this season, prospective moms might be able to share the extra guilt from overindulging on holiday treats with their male counterparts.

I. Donkin et al., Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 10.1016/j.cmet.2015.11.004 (2015). [Abstract]

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