The term “epigenetics” was first coined in 1942 by embryologist Dr. Waddington. It refers to the study of external or environmental factors and their ability to alter gene expression without changing a person’s DNA sequence itself. However, only recently have scientists begun to make strides in understanding the true impact that epigenetics can have on our biology. Researchers at the University of Pennsylvania have discovered that male mice experiencing high levels of stress produce altered sperm, resulting in abnormal brain development and different stress responses in offspring.
Previously, the researchers conducted a study demonstrating that male mice, stressed by exposure to predator odors and changing cages, produced offspring with a weaker response to stress. Additionally, the stressed fathers displayed certain alterations to the genetic material in their sperm. Sperm from stressed fathers, compared to those from unstressed fathers, showed an increased expression of nine miRs, or microRNAs. MicroRNAs are small molecules of RNA, a type of genetic material. Unlike their larger counterparts (mRNA), these microRNAs are tiny molecules that don’t code for proteins. Instead, they play a more subtle role in gene expression, the process by which proteins are formed from the information coded in genes. By binding to target sites on mRNA, miRs can silence certain genes and prevent their expression. This is one example of an epigenetic modification.
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Building off this earlier study, the researchers further explored the relationship between stress and the overexpression of the nine miRs. They injected the miRs into mouse zygotes, which were carried by female surrogates. Once they reached adulthood, the offspring were subjected to mild stress. In response, they produced lower levels of cortisone, a hormone released in response to stress, compared to mice from the control group, resulting in a dampened stress response. A dampened stress response could be potentially harmful for mice in the wild, as they would have weaker responses to predators and other threats in their environments. The offspring also displayed altered gene expression in the paraventricular nucleus, a structure in a brain involved in the regulation of stress responses.
When studying the mechanism by which the miRs affected these changes, the researchers found, post-fertilization, that the miRs were targeting maternal mRNA. This bundle of genetic material, which comes from the mother, is stored in the egg and is responsible for relaying instructions for early development of the zygote. Zygotes injected with the nine miRs showed a reduction in the maternal mRNA levels compared to control zygotes, indicating that the miRs were attacking and degrading the mRNA.
The researchers plan to further study the specific factors involved in the increased expression of miRs and to explore how intervention might prevent the altered stress response in their offspring. In the future, they hope to study miRs in humans to determine if we might pass on stress responses to our children in a similar way.
Feature Image Source: DNA by Miki Yoshihito
