From The Scientist :
Stressed male mice can pass on an abnormal stress response to their offspring via microRNAs found in sperm, a study shows.
Researchers at the University of Pennsylvania led by Tracy Bale have now demonstrated that an increase in a group of microRNAs (miRNAs) in sperm from stressed mice can lead to altered stress response in adult offspring. The work, published today (October 19) in PNAS, shows that simultaneously injecting nine miRNAs into mouse zygotes recapitulates the changes found in the offspring of stressed mice.
“I think it’s a fine paper [and a] well-designed study,” said Michael Skinner, who studies epigenetic inheritance at Washington State University and was not involved in the study. “It shows a very nice role for noncoding RNA at the early embryonic stage for transmission of the transgenerational phenotype.”
Oliver Rando, who studies paternal effects of diet in mammals at the University of Massachusetts Medical School but was not involved in the study, pointed out that the findings reinforce those of another study led by Isabelle Mansuy at the University of Zurich, Switzerland, which showed that injecting sperm RNAs into zygotes recapitulates the transgenerational effects of trauma. This latest study improves on the previous one by identifying specific miRNAs that transmit stress to offspring rather than injecting bulk sperm RNA, Rando said. Further, the new paper shows that injected miRNAs knock down expression of specific genes in zygotes. “That’s probably the really killer addition of this paper relative to previous work,” Rando said. More.
Here’s the abstract:
Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic–pituitary–adrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated long-term reprogramming of the hypothalamic transcriptome with HPA axis dysfunction, noting a marked decreased in the expression of extracellular matrix and collagen gene sets that may reflect an underlying change in blood–brain barrier permeability. We conclude by investigating the developmental impact of sperm miRs in early zygotes with single-cell amplification technology, identifying the targeted degradation of stored maternal mRNA transcripts including sirtuin 1 and ubiquitin protein ligase E3a, two genes with established function in chromatin remodeling, and this potent regulatory function of miRs postfertilization likely initiates a cascade of molecular events that eventually alters stress reactivity. Overall, these findings demonstrate a clear mechanistic role for sperm miRs in the transgenerational transmission of paternal lifetime experiences. (paywall) – A.B. Rogers et al., “Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress,” PNAS, doi:10.1073/pnas.1508347112, 2015
See also: Epigenetic change: Lamarck, wake up, you’re wanted in the conference room!
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