Transgenerational epigenetic inheritance is one hot topic, and it has long been shrouded in skepticism, but a number of cases and mechanistic insights into transgenerational epigenetic inheritance have helped molecular biology move past the limits of genetic determinism. Now a team from the University of Cambridge show that fetal nourishment results in a transgenerational epigenetic effect, rather than true transgenerational epigenetic inheritance.

Senior author Anne Ferguson-Smith shares that “When food is scarce, children may be born ‘pre-programmed’ to cope with undernourishment. In the event of a sudden abundance in food, their bodies cannot cope and they can develop metabolic diseases such as diabetes. We need to understand how these adaptations between generations occur since these may help us understand the record levels of obesity and type 2 diabetes in our society today.”

So the team set out to check out inherited flow across generations of mice, here’s the skinny:

Sperm from in utero undernourished mice (F1) show hypomethylation in 111 regions that are enriched for nucleosome retaining regions.

undernourished mice (F1) show hypomethylation in 111 regions that are enriched for nucleosome retaining regions. The differentially methylated regions (DMRs) tend to cluster in non-coding regions of DNA.

As might be expected, in the grandchildren of the undernourished mice, the genes next to the DMRs were down regulated.

Surprisingly, when looking at the F2 (grandchild) DNA, the methylation changes had disappeared.

This intriguing observation suggests that the potentially heritable marks from a grandmother’s under-nutrition during pregnancy is no longer being transmitted by DNA methylation. Adding to the complexity, a substantial fraction of the DMRs are resistant to early embryo methylation reprogramming, which may be how they impact F2 development while also leaving no DNA methylation signature as it gets erased during later tissue development.

Author Mary-Elizabeth Patti concludes that “This was a big surprise: dogma suggested that these methylation patterns might persist down the generations. From an evolutionary point of view, however, it makes sense. Our environment changes and we can move from famine to feast, so our bodies need to be able to adapt. Epigenetic changes may in fact wear off. This could give us some optimism that any epigenetic influence on our society’s obesity and diabetes problem might also be limited and/or reversible.” Ultimately, this work highlights the importance of a complete follow through in all examination of transgenerational epigenetic inheritance and distinguishing between an intergenerational effect and true inheritance.

Learn all about the complexities of Inheritance in Science, July 2014