Discovery identifies non-DNA mechanisms involved in the transmission of paternal experience to offspring

It has long been known that a parent’s DNA is the primary determinant of health and disease in offspring. However, inheritance through DNA is only part of the story; a father’s lifestyle, such as diet, obesity and stress levels, is associated with health consequences for his offspring. This happens through the epigenome – hereditary biochemical features related to the DNA and the proteins that bind to it. But how the information is transferred at fertilization, along with the exact mechanisms and molecules in sperm involved in this process, has been unclear until now.

A new study from McGill, recently published in Development cell, has made significant progress in the field by identifying how environmental information is conveyed by non-DNA molecules in the sperm. It is a discovery that advances scientific understanding of the heredity of paternal life experiences and potentially opens new avenues for studying disease transmission and prevention.

A paradigm shift in the understanding of heredity

“The big breakthrough with this study is that it has identified a non-DNA-based agent that allows sperm to memorize a father’s environment (diet) and transmit that information to the embryo,” said Sarah Kimmins, Ph.D., the senior. author of the study and the Canada Research Chair in Epigenetics, Reproduction and Development. The paper builds on her group’s 15 years of research. “It’s remarkable, as it shows a major shift from what is known about heredity and disease from DNA-based only to one that now contains sperm proteins. This study opens the door to the possibility that the key to understanding and preventing certain diseases may include proteins in semen. “

“When we first started to see the results, it was exciting because no one has previously been able to track how those hereditary environmental signatures are transferred from the sperm to the embryo,” adds Ph.D. candidate Ariane Lismer, the lead author on paper. “It was especially rewarding because it was very challenging to work at the molecular level of the embryo, just because you have so few cells available for epigenomic analysis. It’s only thanks to new technology and epigenetic tools that we get to these results.”

Changes in sperm proteins affect the offspring

To determine how information influencing development is passed on to embryos, the researchers manipulated the sperm epigenome by feeding male mice a low-folic acid diet and then tracing the effects on certain groups of molecules in proteins associated with DNA.

They found that diet-induced changes in a particular group of molecules (methyl groups) associated with histone proteins (which are crucial in packaging DNA into cells) led to changes in gene expression in embryos and birth defects of the spine and skull. . Interestingly, the changes in the methyl groups on the histones in the sperm were transferred at fertilization and remained in the developing embryo.

“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,” adds Kimmins. “The hope that this work offers is that by expanding our understanding of what is inherited beyond just DNA, there are now potentially new avenues for disease prevention that will lead to healthier children and adults.”