Studies in mammals have shown that the ‘memories’ of various environmental effects – such as diet, weight and stress – are passed on from father to offspring, although these conditions are not encoded in the DNA sequences carried by the sperm. Now we have a new explanation for how this is possible.
The story has a lot to do with epigenetics. Molecules that attach themselves to DNA can act as on-off switches that determine which parts of DNA are used – but until now we do not know which of these molecules can carry the institutions that are characterized by a father’s life experiences, to in an embryo via sperm.
“The major breakthrough with this study is that it identified a non-DNA-based agent on which sperm remember the environment of a father (diet) and transmit the information to the embryo,” said Sarah Kimmins, epigeneticist of McGill University, said.
Using mice, epigeneticist Ariane Lismer and colleagues were able to show that the effects of a folate deficiency diet could be transmitted by altering histone molecules in the sperm. Simply put, histones are really basic proteins that turn DNA around for a tangle-free storage.
When mammals build sperm in mammals, they shed most of the histone coils so that they can be packed tighter.
But there is still a small percentage (1 percent in mice and 15 percent in humans) that provide DNA scaffolds in regions specific for spermatogenesis and function, metabolism and embryo development – to enable the cellular mechanisms to use these DNA instructions.
Chemical adaptation of these histones – the most common form of methylation – is what enables or prevents the DNA from being ‘read’ so that it can be transcribed into protein products. Poor diet can cause these histones to change their methylation status.
This is why we hear how important folate is for women during pregnancy: A mother’s folate helps stabilize DNA methylation in their young.
By feeding male mice a lack of folate from weaning, the researchers were able to detect the changes in histones from the male’s sperm and in the resulting embryos. And indeed, sperm histone changes were also present in the developing embryo.
“No one has been able to detect beforehand how those hereditary environmental signatures are transferred from the sperm to the embryo,” Lismer said.
The team also discovered that these effects can be cumulative and can lead to an increase in the severity of birth defects.
Interestingly, the congenital abnormalities that occur in mice, including underdevelopment at birth and spinal disorders, are well documented in folate deficiencies in humans.
The researchers hope that expanding our knowledge of hereditary mechanisms will reveal new ways to treat and prevent such conditions. But there is still a lot to work out before then.
“Our next steps will be to determine if these harmful changes in sperm proteins (histones) can be repaired. We have new exciting work that suggests this is indeed the case,” Kimmins said.
This research was published in Development cell.