Big idea
According to a recently published study, sperm from older rats differs from sperm from young rats in that they can affect embryonic development.
Sperm not only have genes, but also instructions that determine which genes are turned on or off in the offspring. These directions are Epigenetic information..
In the rats we studied, age had a significant effect on the activity of many genes in sperm. In particular, we found that age affects two epigenetic mechanisms. DNA methylationChemically alter DNA to block specific genes, Small RNAAnother method of gene silencing.
Important reason
In developed countries, people are giving birth to their first child more late than ever.In the United States, the number of male children of fathers between the ages of 35 and 44 50% increase over the last 30 years.. The disadvantage of this tendency is that children pregnant by older fathers are at increased risk of poor health.
These conditions include various formats cancer, schizophrenia, Autism spectrum disorder, Bipolar disorder When Attention deficit / hyperactivity disorderAbove all.
It is now clear that the quality of information transmitted by sperm declines with age.However, these changes Accumulation of mutations or some other mechanism.. Our rat data suggest that epigenetic changes are one cause.
How to work
In our experiment, we collected sperm from 65-day-old and 120-day-old rats. These ages correspond to humans approximately 20-25 and 40-45 years. Analysis of the sperm of these animals using methods based on DNA sequencing revealed that the sperm of older rats had a very different epigenetic profile (or operating procedure) than that of younger rats. rice field.
In older rats, different levels of methylation were found at 5,319 DNA sites. This is an epigenetic mechanism that occurs when: Addition of methyl group (-CH3) to DNA..but A single instance of methylation can result in switching off nearby genesThe number of sites we have found is sufficient to affect 5% of all rat genes.
Old rat sperm also differed in the concentration of small RNA, a large class of small molecules that could interfere with gene expression.3.6% of the total Identified small RNA It was different in older rats. Similar to DNA methylation, changes in small RNA Activity of multiple genes..
Computational algorithms were used to identify genes affected by these epigenetic mechanisms. 3,066 was regulated by DNA methylation and 4,950 was regulated by small RNA. Significant duplication.. Most of the genes we have identified regulate embryogenesis, including the development of the brain and other organs.
Our study analyzed only sperm – it did not study offspring. However, knowing which genes are likely to be turned off and their specific function can confidently predict what will go wrong with the development of the rat’s offspring that the older mouse has become a father. I can do it. If the same mechanism is present in humans, epigenetic changes in sperm may be partially involved in the greater risk of certain health conditions in children pregnant by older fathers.
What is not yet known
New research show Similar age-related changes occur in human sperm.. However, epigenetic research on human sperm is still in its infancy. Unlike fixed genetic information, epigenetic information is flexible and Changes due to many lifestyles and environmental factors.. My colleagues and I hope that our research will help develop future therapies that can address the health of children before they become pregnant.
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This article will be republished from conversation, A non-profit news site aimed at sharing ideas from academic experts. It was written by: Alexander Suvorov, University of Massachusetts Amherst..
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Alexander Suvorov is funded by the National Science Foundation of the United States and the Russian Science Foundation. I am affiliated with the Institute of Physical Chemistry and Biology at Moscow State University.