Parental Environment May Have Impact on Future Generations, Says Study

In a study published online this week in the journal eLife, researchers from the Geisel School of Medicine at Dartmouth examined how environmental stressors put on fruit flies (Drosophila melanogaster) can influence the phenotypes of their offspring.

A fruit fly (Drosophila melanogaster). Image credit: Sanjay Acharya / CC BY-SA 4.0.

“While neuronally encoded behavior isn’t thought to be inherited across generations, we wanted to test the possibility that environmentally triggered modifications could allow ‘memory’ of parental experiences to be inherited,” said Julianna Bozler, first author of the study.

When exposed to parasitoid wasps — which deposit their eggs into and kill the larvae of fruit flies — females of Drosophila melanogaster are known to shift their preference to food containing ethanol as an egg laying substrate, which protects their larvae from wasp infection.

For the study, the fruit flies were cohabitated with female wasps for four days before their eggs were collected.

The embryos were separated into two cohorts — a wasp-exposed and unexposed (control) group — and developed to maturity without any contact with adult flies or wasps.

One group was used to propagate the next generation and the other was analyzed for ethanol preference.

Model for fly-wasp mediated ethanol preference: a female fly encounters a wasp, based in part on visual signals, leading to a cascade of physiological and behavioral changes; one of the initiating factors following wasp exposure is the depression of NPF in the female fly brain; under normal conditions, NPF inhibits the ethanol preference behavior and caspase mediated germline apoptosis; therefore, the reduction of NPF triggers ethanol preference and germline caspases; activation of the germline effector caspases Dcp-1 and Drice in turn reduced egg laying and participates in the epigenetic reprograming of the female germline and chromosome 3; the epigenetic program is passed to both sexes of the F1 generation, in that both male and female progeny can pass on the ethanol preference; further, legacy F1 female flies inherit depressed NPF in the fan shaped body (FSB), which drives the ethanol preference behavior. Model legend: measured behavioral outputs are in blue, the dashed lines indicate a speculative or unknown mechanism of action. Image credit: Bozler et al, doi: 10.7554/eLife.45391.

“We found that the original wasp-exposed flies laid about 94% of their eggs on ethanol food, and that this behavior persisted in their offspring, even though they’d never had direct interaction with wasps,” Bozler explained.

The ethanol preference was less potent in the first-generation offspring, with 73% of their eggs laid on ethanol food.

“But remarkably, this inherited ethanol preference persisted for five generations, gradually reverting back to a pre-wasp exposed level. This tells us that inheritance of ethanol preference is not a permanent germline change, but rather a reversible trait,” Bozler said.

Importantly, the team determined that one of the critical factors driving ethanol preference behavior is the depression of Neuropeptide-F (NPF) that is imprinted in a specific region of the female fly’s brain.

While this change, based in part on visual signals, was required to initiate transgenerational inheritance, both male and female progeny were able to pass on ethanol preference to their offspring.

“We hope that our findings may lead to greater insights into the role that parental experiences play across generations in diseases such as drug and alcohol disorders,” said Professor Giovanni Bosco, senior author of the study.

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Julianna Bozler et al. 2019. Transgenerational inheritance of ethanol preference is caused by maternal NPF repression. eLife 8: e45391; doi: 10.7554/eLife.45391