How the sperm are remembered | Writing

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It has long been known that the DNA of a parent is the primary determinant of the health and disease of the offspring. Yet inheritance via DNA is only part of the story; a father’s lifestyle, such as diet, overweight and stress levels, have been linked to health consequences for his offspring. It happens through the epigenome – inherited biochemical markings associated with DNA and the proteins that bind to it. But how information is transmitted during fertilization as well as the exact mechanisms and molecules in the sperm involved in this process have not been clear until now.

A new McGill study, recently published in Development cell, has made a significant breakthrough in the field by identifying how environmental information is transmitted by non-DNA molecules in semen. It’s a discovery that advances scientific understanding of the inheritance of paternal life experiences and potentially opens up new avenues for studying disease transmission and prevention.

A paradigm shift in the understanding of heredity

“The great advancement of this study is that it identified a non-DNA-based way by which sperm remember a father’s environment (diet) and pass this information on to the embryo,” explains Sarah Kimmins, PhD, lead author of the study and the Canada Research Chair in Epigenetics, Reproduction and Development. The article is based on 15 years of research by his group. “This is remarkable because it presents a major shift from what is known about heritability and disease to be based solely on DNA, to one which now includes semen proteins. This study opens the door to the possibility that the key to understanding and preventing certain diseases could involve protein in semen. “

“When we started to see the results, it was exciting because no one had been able to track how these hereditary environmental signatures are passed from sperm to embryo before,” adds doctoral student Ariane Lismer, the first author. of the article. “It was especially rewarding because it was very difficult to work at the molecular level of the embryo, simply because you have so few cells available for epigenomic analysis. It is only thanks to new technologies and epigenetic tools that we have been able to achieve these results.

Changes in semen proteins affect the offspring

To determine how information that affects development is transmitted to embryos, the researchers manipulated the sperm epigenome by feeding male mice a low-folate diet and then tracing the effects on particular groups of molecules in the associated proteins. to DNA.

They found that diet-induced changes in a certain group of molecules (methyl groups), associated with histone proteins (which are essential for packaging DNA in cells), lead to alterations in gene expression. in embryos and congenital malformations of the spine and skull. . What was remarkable was that the changes in the methyl groups on the histones of the sperm were transmitted during fertilization and remained in the developing embryo.

“Our next steps will be to determine whether these harmful changes induced in semen proteins (histones) can be repaired. We have exciting new work that suggests this is indeed the case, ”Kimmins adds. “The hope offered by this work is that by expanding our understanding of what is inherited beyond DNA, there are now potentially new pathways to disease prevention that will lead to healthier children and adults. . “

About this study:

“The trimethylation of histone H3 lysine 4 in sperm is transmitted to the embryo and associated with food-induced phenotypes in the offspring” by Ariane Lismer et al in Development cell

https://doi.org/10.1016/j.devcel.2021.01.01

The research was funded by the Canadian Institutes of Health Research


About McGill University

Founded in Montreal, Quebec, in 1821, McGill University is the best medical doctoral university in Canada. McGill is consistently ranked among the top universities, both nationally and internationally. It is a world-renowned higher education institution with research activities spanning two campuses, 11 faculties, 13 vocational schools, 300 study programs and over 40,000 students, including over 10,200 graduate students. McGill attracts students from over 150 countries around the world, with its 12,800 international students representing 31% of the student body. More than half of McGill students report having a mother tongue other than English, including about 19% of our students who say French is their mother tongue.


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