We know that the 'memories' of various environmental effects – such as diet, weight, and stress – can be passed on from fathers to offspring, despite these effects not being coded for in the DNA sequences carried by sperm.

We now have an explanation for how it's possible: epigenetics.

Molecules that attach themselves to DNA can act like on-off switches that control which sections of DNA get used – but until 2021, we didn't know which of these molecules can carry the settings marked by a father's life experiences, to be incorporated into an embryo via sperm.

The big breakthrough came with a new study - it has identified a non-DNA-based means by which sperm remember a father's environment (diet) and transmit that information to the embryo. Using mice, epigeneticists were able to demonstrate that the effects of a folate-deficient diet could be passed on by altering histone molecules in sperm. Simply put, histones are really basic proteins that DNA winds around for tangle-free storage.

In mammals, when male bodies build sperm, they throw out most of the histone spools, to allow for tighter packing.

But a small percentage still remains (1 percent in mice and 15 percent in humans), providing scaffolding for DNA in regions specific to sperm creation and function, metabolism, and embryo development – to allow the cellular mechanisms to make use of these DNA instructions.

Chemical modification of these histones – the most common form being methylation – is what allows or prevents the DNA to be 'read' so that it can be transcribed into protein products. Poor diet can cause these histones to change their methylation status. This is why we hear about the importnace of folate for women during pregnancy: A mother's folate helps stabilize DNA methylation in their young.

By feeding male mice a folate-deficient diet from the time they were weaned, the researchers were able to track the changes to histones from the male's sperm and in the resulting embryos. And indeed, sperm histone changes were also present in the developing embryo.

 also discovered these effects could be cumulative and lead to an increase in the severity of birth defects.

Interestingly, the birth defects seen in the mice, including underdevelopment at birth and spinal abnormalities, are well documented in folate-deficient human populations.

The researchers hope that expanding our knowledge of inheritance mechanisms will reveal additional ways to treat and prevent such conditions.

https://www.cell.com/developmental-cell/fulltext/S1534-5807(21)00072-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1534580721000721%3Fshowall%3Dtrue

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What Your Father Did Before You Were Born Could Influence Your Future Health

It might not just be expectant mothers who have to pay attention to their lifestyle.

Now a  study published in Science could be relevant to a growing body of research looking at ways in which the lifestyle and environment of men before they become fathers could influence the lives of their children and grandchildren.

We know that many human traits, such as weight, height, susceptibility to disease, longevity or intelligence, can be partly inherited, but researchers have so far struggled to identify the precise genetic basis for this. This may partly be due to limitations in our understanding of how genetics works, but now there is growing interest in the potential for something called epigenetics to explain this heritability.

Epigenetics refers to the information in the genome over and above that contained in the DNA sequence. This information takes a number of forms, but the most popular ones scientists have studied relate to the chemical modification (known as methylation and acetylation) of DNA and the proteins called histones that together make up the human genome.

This epigenetic information - which influences which copies of the genes in our DNA are 'expressed', or used - may be passed from one generation to another during reproduction. It can even persist within a lifetime in a person's tissues and organs, even as their cells are replenished.

There has been much interest in recent years in the possibility that a person's environment during reproduction, such as their nutrition, can influence the 'epigenetic signatures' in their children - potentially with consequences for health later in later life.

Most studies have focused on epigenetic signatures passed on through the maternal line. But the mother's genetic material accounts for only half of a child's genome and researchers are increasingly looking at the importance of fathers in the process of epigenetic inheritance. This study* in Science claims to have shown that manipulation of the epigenetic process during the production of sperm in mice influences the development of their offspring over multiple generations.

*  https://www.science.org/doi/10.1126/science.aab2006