Heat induces multiomic and phenotypic stress propagation in zebrafish embryos

Lauric Feugere; Adam Bates; Timothy Emagbetere; Emma Chapman; Linsey E Malcolm; Kathleen Bulmer; Jörg Hardege; Pedro Beltran-Alvarez; Katharina C Wollenberg Valero

doi:10.1093/pnasnexus/pgad137

Heat induces multiomic and phenotypic stress propagation in zebrafish embryos

PNAS Nexus. 2023 May 23;2(5):pgad137. doi: 10.1093/pnasnexus/pgad137. eCollection 2023 May.

Authors

Lauric Feugere¹, Adam Bates^{1

2}, Timothy Emagbetere¹, Emma Chapman¹, Linsey E Malcolm³, Kathleen Bulmer³, Jörg Hardege¹, Pedro Beltran-Alvarez³, Katharina C Wollenberg Valero⁴

Affiliations

¹ Department of Biological and Marine Sciences, University of Hull, Kingston upon Hull HU6 7RX, UK.
² Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
³ Biomedical Institute for Multimorbidities, Centre for Biomedicine, Hull York Medical School, University of Hull, Kingston upon Hull HU6 7RX, UK.
⁴ School of Biology and Environmental Science, University College Dublin, Belfield Dublin 4, Ireland.

Abstract

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecular signatures of this process, by integrating multiomic and phenotypic data. In individual zebrafish embryos, repeated heat peaks elicited both a molecular response and a burst of accelerated growth followed by a growth slowdown in concert with reduced responses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolites including sulfur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signaling, glycosaminoglycan/keratan sulfate, and lipid metabolism. Consequently, non-heat-exposed receivers (exposed to stress metabolites only) experienced accelerated catch-up growth in concert with reduced swimming performance. The combination of heat and stress metabolites accelerated development the most, mediated by apelin signaling. Our results prove the concept of indirect heat-induced stress propagation toward naive receivers, inducing phenotypes comparable with those resulting from direct heat exposure, but utilizing distinct molecular pathways. Group-exposing a nonlaboratory zebrafish line, we independently confirm that the glycosaminoglycan biosynthesis-related gene chs1 and the mucus glycoprotein gene prg4a, functionally connected to the candidate stress metabolite classes sugars and phosphocholine, are differentially expressed in receivers. This hints at the production of Schreckstoff-like cues in receivers, leading to further stress propagation within groups, which may have ecological and animal welfare implications for aquatic populations in a changing climate.

Keywords: multiomics; stress cues; stress propagation; stress response; thermal stress.