Zebrafish Moms May Protect Eggs from Stress with Hormone that Reduces Cell Death
By Michael Lim
21 November 2018
All parents want to protect their unborn children – and with good reason. Exposure to stress can activate signaling pathways that lead to increased cell death in developing offspring, which may affect their survival. New work by Drs. Sarah Alderman and Nicholas Bernier in the Department of Integrative Biology reveals that female zebrafish may be able to reduce stress-induced programmed cell death in their embryos by depositing the hormone CRF into their eggs.
CRF, or corticotropin releasing factor, is a hormone best known for its role in the stress response. Produced in the brain, CRF normally signals the production of another type of hormone – glucocorticoids – which help mobilize energy stores to deal with stressors. When a zebrafish mother is exposed to stress, it can lead to deposition of CRF mRNA into her eggs, which codes for the production of CRF. However, early in development, embryos are unable to use CRF to produce glucocorticoids. This interesting observation poses the question: why do mothers give CRF mRNA to their offspring if they can’t use it for the stress response cascade?
“I was curious about why CRF mRNA was present, and what was happening,” says Alderman. “Early in development many things are turning on, shutting off – it’s an exciting time.”
With the help of two undergraduate research assistants, Emily Leishman and Meghan Fuzzen, Alderman set out to examine the potential role of CRF in early development by injecting zebrafish embryos with either CRF or a blank control, and then exposing them to a heat shock. Embryos injected with CRF had a smaller increase in caspase-3 activity, a compound that leads to programmed cell death.
Going a step further, Alderman and her team also treated embryos with a drug that blocks CRF receptors, and observed a significant increase in caspase-3 activity following a heat shock compared to control embryos. This suggests that increased CRF deposits from mothers may be able to blunt the induction of programmed cell death in their offspring.
Alderman notes that while not all programmed cell death is inherently bad, exposure to stress can lead to a potentially harmful increase in the amount of cells dying; thus, zebrafish mothers may be lending a protective benefit to their offspring by depositing CRF mRNA in eggs.
The study provides two other important messages. The first is that CRF has a notable role outside glucocorticoid production. The second message may not be as obvious: the importance of curiosity, serendipity, and undergraduate researchers in science.
“This study was a several year adventure,” says Alderman. “What started out as a curious observation of CRF mRNA in embryos expanded into a full project, and it could not have been done without our undergraduate students. Undergraduate research matters!”
Alderman recommends that future research into this phenomenon include observing development and behavior in zebrafish offspring with elevated CRF levels, and examining what role elevated CRF may play in other species.
Funding for this research came from the Natural Sciences and Engineering Research Council of Canada.
Read the full article in the journal General and Comparative Endocrinology.
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