Study documents paternal transmission of epigenetic memory via sperm

Studies on human populations and animal models suggest that a father's experiences, such as his diet or environmental stress, may affect the health and development of his offspring. How these effects are transmitted from one generation to the next, however, remains mysterious.

Susan Strome's laboratory at the University of Santa Cruz is progressing regularly in discovering the mechanisms behind this phenomenon, using a tiny round worm called Caenorhabditis elegans show how markings on chromosomes that affect gene expression, called "epigenetic" marks, can be passed from parents to offspring. The last article of his team, published on October 17 in Nature Communications, focuses on the transmission of epigenetic marks by C. elegans sperm.

In addition to documenting the transmission of epigenetic memory by sperm, the new study shows that the epigenetic information provided by sperm cells to the embryo is both necessary and sufficient to guide the proper development of germ cells in offspring (germ cells giving birth to).

"We decided to watch C. elegans because it's a great model for asking epigenetic questions using powerful genetic approaches, "said Strome, a distinguished professor of molecular, cellular and developmental biology.

Epigenetic changes do not alter the gene's DNA sequences, but rather involve chemical modifications of the DNA itself or histone proteins with which the DNA is encapsulated in the chromosomes. These modifications influence the expression of genes, activating or deactivating genes in different cells and at different stages of development. The idea that epigenetic modifications can cause changes in the expression of genes passed down from one generation to the next, called "transgenerational epigenetic inheritance", is now the object. from an intense scientific inquiry.

For many years, it was thought that sperms did not retain any histone packaging and therefore could not transmit histone-based epigenetic information to their offspring. Recent studies, however, have shown that approximately 10% of histone packaging is retained in sperm in humans and mice.

"In addition, where chromosomes retain histone, DNA is present in areas of importance for development, so these findings have raised public awareness of the possibility that sperm transmits important epigenetic information to embryos, "said Strome.

When his lab looked C. elegans sperm, the sperm genome fully retains the packing of histones. Other researchers have discovered that the same goes for another commonly studied organism, the zebrafish.

"Like zebrafish, worms represent an extreme form of histone retention by sperm, making it an excellent system to see if this packaging is really important," said Strome.

His lab is focused on a particular epigenetic brand (called H3K27me3) that has been well established as a hallmark of repressed gene expression in a wide range of organisms. The researchers found that removing this mark from sperm chromosomes makes the majority of the offspring sterile. After establishing that the mark is important, they wanted to know if it was sufficient to guide the normal development of the germ line.

The researchers addressed this issue by analyzing a mutant worm in which the chromosomes of the sperm and egg are separated in the first cell division after fertilization, so that an embryo cell inherits only sperm chromosomes and embryo cell inherits chromosomes from the egg and sperm). This unusual pattern of chromosome segregation allowed researchers to generate worms whose germ line inherited only sperm chromosomes and therefore only epigenetic sperm marks. These worms have been shown to be fertile and have normal gene expression patterns.

"These results show that the packaging of DNA in sperm is important because offspring that did not inherit normal epigenetic sperm marks were sterile and sufficient for the development of the sperm." a normal germ line, "said Strome.

Although the study shows that epigenetic information transmitted by sperm is important for normal development, they do not directly address how the life experience of a father can affect the health of his descendants. Strome's lab is studying this issue with the help of experiments in which worms are treated with alcohol or are hungry before they reproduce.

"The goal is to analyze how the conditioning of chromatin changes in the parent," she said. "Everything that is transmitted to the offspring has to go through the germ cells – we want to know which cells are undergoing the environmental factors, how are they transmitting this information to the germ cells, what changes in the germ cells, and how that affects the offspring."

By demonstrating the importance of sperm-mediated epigenetic information, the present study establishes that if the father's environment alters the epigenetic chromosomes of sperm, it could affect offspring.

Explore further:
Study shows how epigenetic memory is passed from generation to generation

More information:
Tomoko M. Tabuchi et al., Sperm cells of Caenorhabditis elegans carry an epigenetic memory based on histones of spermatogenesis and oogenesis, Nature Communications (2018). DOI: 10.1038 / s41467-018-06236-8