How sperm remember
It has long been understood that a parent鈥檚 DNA is the principal determinant of health and disease in offspring. Yet inheritance via DNA is only part of the story; a father鈥檚 lifestyle such as diet, being overweight and stress levels have been linked to health consequences for his offspring. This occurs through the epigenome - heritable biochemical marks associated with the DNA and proteins that bind it. But how the information is transmitted at fertilization along with the exact mechanisms and molecules in sperm that are involved in this process has been unclear until now.
A new study from 捆绑SM社区, published recently in , has made a significant advance in the field by identifying how environmental information is transmitted 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 understanding of heredity
鈥淭he big breakthrough with this study is that it has identified a non-DNA based means by which sperm remember a father鈥檚 environment (diet) and transmit that information to the embryo,鈥� says Sarah Kimmins, PhD, the senior author on the study and the Canada Research Chair in Epigenetics, Reproduction and Development. The paper builds on 15 years of research from her group. 鈥淚t 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.鈥�
鈥淲hen 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,鈥� adds PhD candidate Ariane Lismer, the first author on the paper. 鈥淚t 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.鈥�
Changes in sperm proteins affect offspring
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 (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. What was remarkable was that the changes to the methyl groups on the histones in sperm were transmitted at fertilization and remained in the developing embryo.
鈥淥ur next steps will be to determine if these harmful changes induced in the sperm proteins (histones) can be repaired. We have exciting new work that suggest that this is indeed the case,鈥� adds Kimmins. 鈥淭he 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.鈥�
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About this study: 鈥淗istone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring鈥� by Ariane Lismer et al in The research was funded by the Canadian Institute of Health Research |
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About 捆绑SM社区
Founded in Montreal, Quebec, in 1821, 捆绑SM社区 is Canada鈥檚 top ranked medical doctoral university. 捆绑SM社区 is consistently ranked as one of the top universities, both nationally and internationally. It鈥痠s a world-renowned鈥痠nstitution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. 捆绑SM社区 attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of 捆绑SM社区 students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.
