Mammal studies have shown that the ‘memories’ of various environmental effects – such as nutrition, weight and stress – are passed from fathers to offspring, even though these states are not encoded in the DNA sequences carried by sperm. Now we have a new explanation for how it is possible.
The story has a lot to do with epigenetics. Molecules that attach to the DNA can act as on / off switches that control which parts of the DNA are used – but so far we don’t know which of these molecules can carry the settings marked by a father’s life experiences , to be introduced into an embryo via semen.
“The big breakthrough with this study is that it has identified a non-DNA-based agent that allows sperm to memorize the environment (diet) of a father and transmit that information to the embryo,” said Sarah Kimmins, McGill University epigeneticist.
Using mice, epigeneticist Ariane Lismer and colleagues were able to demonstrate that the effects of a low-folic acid diet could be passed on by turning histone molecules in sperm. Simply put, histones are basically basic proteins that the DNA wraps around for tangle-free storage.
In mammals, when male bodies build up sperm, they discard most of the histone coils to allow for a tighter packing.
But a small percentage remains (1 percent in mice and 15 percent in humans) that scaffolds for DNA in regions specific to sperm production and function, metabolism, and embryo development – so that the cellular mechanisms are used. can make these DNA instructions.
Chemical modification of these histones – the most common form is methylation – causes or prevents the DNA from being ‘read’ so that it can be transcribed into protein products. Due to a poor diet, these histones can change their methylation status.
This is why we hear about the importance of folic acid to women during pregnancy: a mother’s folic acid helps stabilize DNA methylation in their young.
Feeding male mice a low-folate diet from the time they were weaned allowed the researchers to monitor the changes in histones from the male sperm and into the resulting embryos. Indeed, changes in the sperm histone were also present in the developing embryo.
“No one has previously been able to figure out how those hereditary environmental signatures are transferred from the sperm to the embryo,” said Lismer.
The team also found that these effects can be cumulative and lead to an increase in the severity of birth defects.
Interestingly, the birth defects observed in the mice, including underdevelopment at birth and spinal abnormalities, are well documented in folic acid deficient human populations.
The researchers hope that expanding our knowledge of inheritance mechanisms will reveal new ways to treat and prevent such conditions. But a lot more needs to be worked out before then.
“Our next steps will be to determine whether these deleterious changes induced in the sperm proteins (histones) can be repaired. We have exciting new work suggesting that this is indeed the case,” said Kimmins.
This research is published in Development cell