The Research Summary is a brief summary of interesting academic papers.
The big idea
The sperm of older mice differs from that of younger mice in a way that can affect the development of the embryo, according to research published recently.
The sperm carries not only genes, but also instructions that determine which genes will be activated or deactivated in the offspring. These directions are known as epigenetic information.
In the mice we studied, age had a profound effect on the activity of many sperm genes. We found that age affected two epigenetic mechanisms in particular: DNA methylation, which chemically alters DNA to block specific genes, and small RNA, another method of gene silencing.
Why does it matter
In developed countries, people are having their first child later than ever. In the United States, the number of men between the ages of 35 and 44 who are parents has increased by 50% in the past three decades. A disadvantage of this trend is that children conceived by older parents are at increased risk of adverse health problems.
These conditions include different forms of cancer, schizophrenia, autism spectrum disorder, bipolar disorder and attention deficit / hyperactivity disorder, among others.
It is now clear that the quality of the information transferred by the sperm decreases with age. We do not yet know, however, whether these changes occur through an accumulation of mutations or some other mechanism. Our data from rats suggest that epigenetic changes are one of the culprits.
How we do our work
In our experiments, we collected sperm from rats aged 65 and 120 days. These ages correspond approximately to humans aged 20 to 25 and 40 to 45 years of age. We analyzed the sperm from these animals using methods based on DNA sequencing and found that the sperm from older mice had epigenetic profiles – or operating instructions – very different from those in younger mice.
In older mice, 5,319 DNA sites had different levels of methylation, an epigenetic mechanism that occurs when the methyl group (-CH3) is added to DNA. Since even single occurrences of methylation can result in the shutdown of nearby genes, the number of sites we find is sufficient to affect 5% of all mouse genes.
Sperm from older mice also had different concentrations of small RNAs, which are a large class of tiny molecules that can interfere with gene expression. We found that 3.6% of all small RNAs identified were different in older mice. Like DNA methylation, changes in the small RNA can affect the activities of several genes.
Using computational algorithms, we identified the genes affected by these epigenetic mechanisms – 3,066 were regulated by DNA methylation and 4,950 by small RNA, with significant overlap. Most of the genes we have identified regulate embryonic development, including that of the brain and other organs.
Our study looked at sperm only – it did not study offspring. But knowing which genes are likely to be deactivated – and their specific functions – allows us to safely predict what will go wrong in the development of baby mice born to older mice. If the same mechanism exists in humans, epigenetic changes in sperm may be partly responsible for the increased risk of certain health conditions in children conceived by older parents.
What is not yet known
Emerging research shows that similar age-related changes occur in human sperm. But the epigenetic study of human sperm is in its infancy. Unlike genetic information, which is fixed, epigenetic information is highly flexible and can be altered by many lifestyles and environmental factors. My colleagues and I hope that our research will help develop future therapies that can take care of children’s health even before they are conceived.
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This article was republished from The Conversation, a non-profit news site dedicated to sharing ideas from academic experts. It was written by: Alexander Suvorov, University of Massachusetts Amherst.
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Alexander Suvorov receives funding from the US National Science Foundation, the Russian Science Foundation. I have an adjunct affiliation with the Institute of Physical-Chemical Biology at Moscow State University,