Dr. Elizabeth Radford discusses some of the latest trends in intergenerational epigenetic inheritance. This interview was shot at the Keystone Symposia’s meeting on Nutrition, Epigenetics and Human Disease, 2013 held in Santa Fe, New Mexico
Intergenerational Epigenetic Inheritance
We’re collaborating with Mary-Elizabeth Patti who works at Harvard, and she has a mouse model where they undernourish during the late stages of pregnancy. And in the offspring they see diabetes, basically, and other metabolic perturbations. And that’s very well established, that’s been replicated by lots of people. But what’s really, really interesting from our point of view as epigeneticists, is that she– well, we see transmission of that phenotype to the next generation. And that occurs through both the maternal line and the paternal line.
And through the maternal line, you know, mum, in utero environment, her metabolism will have a direct impact on the offspring. So although there might be epigenetic inheritance at play, it’s very difficult to distinguish that from a sort of environmental, metabolic effect that could recapitulate the original insult of metabolism or cause a different insult. Which then has a similar outcome in the offspring.
“…we can be very certain that it’s an epigenetic factor that’s being transmitted through the sperm of these mice.”
But, the guys– male mice don’t contribute anything more than their sperm to their offspring. So, the only thing that can be– the only causative factor there can be either genetic or epigenetic inheritance. And, because of the way these experiments are done, we can be very certain that it’s an epigenetic factor that’s being transmitted through the sperm of these mice.
So what we’ve done is we’ve taken the sperm of males who were themselves undernourished in utero, and we are trying to profile– carry out an epigenetic profile of their sperm, compared to males who weren’t undernourished when they were in utero. We think that the in utero undernourishment might be really important because your germ cells– your eggs and your sperm– the stem cells that form those are developing when you are yourself unborn. So when you’re in utero.
So they are actually being exposed to the undernourishment. So we are trying to work out which epigenetic modality might be responsible for that. And, obviously, that’s a big ask. And also, where in genome this might be happening.