How do sperm transmit paternal experience to embryos?

A Canadian research team, led by McGill University, has successfully identified how environmental information is transmitted by non-DNA molecules in the sperm. Published in the journal Developmental Cell, their study advances our scientific understanding of the heredity of paternal life experiences and potentially opens new avenues for studying disease transmission and prevention.

It has long been understood that a parent’s DNA is the principal determinant of health and disease in offspring, yet inheritance via DNA is only part of the story. A father’s lifestyle, including diet, weight and stress levels, has been linked to health consequences for his offspring via the epigenome — heritable biochemical marks associated with the DNA and proteins that bind it. But exactly how this information is transmitted at fertilisation, along with the exact mechanisms and molecules in sperm that are involved in this process, has been unclear until now.

“The big breakthrough with this study is that it has identified a non-DNA based means by which sperm remember a father’s environment (diet) and transmit that information to the embryo,” said Dr Sarah Kimmins, the senior author on the study, which builds on 15 years of research from her group at McGill. “It is remarkable, as it presents a major shift from what is known about heritability and disease from being solely DNA-based, to one that now includes sperm proteins. This study opens the door to the possibility that the key to understanding and preventing certain diseases could involve proteins in sperm.”

To determine how information that affects development gets passed on to embryos, the researchers manipulated the sperm epigenome by feeding male mice a folate-deficient diet and then tracing the effects on particular groups of molecules in proteins associated with DNA. They found that diet-induced changes to a certain group of molecules called methyl groups, associated with histone proteins (which are critical in packing DNA into cells), led to alterations in gene expression in embryos and birth defects of the spine and skull. The changes to the methyl groups on the histones in sperm were transmitted at fertilisation and remained in the developing embryo.

“When we first started seeing the results it was exciting, because no one has been able to track how those heritable environmental signatures are transmitted from the sperm to the embryo before,” said McGill PhD candidate Ariane Lismer, first author on the 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 is only thanks to new technology and epigenetic tools that we were able to arrive at these results.”

“Our next steps will be to determine if these harmful changes induced in the sperm proteins (histones) can be repaired,” Dr Kimmins said. “We have exciting new work that suggests that this is indeed the case.

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

Image credit: ©stock.adobe.com/au/Christoph Burgstedt

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