Valero, K. C. W. | Search bioRxiv

bioRxiv2023

Consequences of directly- and indirectly-experienced heat stress in a mutagenic environment

Climate change increases the frequency and duration of heat events. Negative effects of heat stress may be exacerbated through the action of social metabolites between aquatic animals. Whilst early life stages are vulnerable to stress-induced damage, they deploy cellular mechanisms to protect cells against mutagens such as ultraviolet rays (UV). Little is known about the fate of fish embryos which have experienced heat stress in a mutagenic environment. The present study exposed zebrafish embryos to one of three stress history treatments consisting of direct heat stress (TS+UV), the social context of heat stress via social metabolites (SM+UV), and their combination in TS+SM+UV before a UVB/UVA damage/repair assay. We measured phenotypic and transcriptomic responses to these treatments, and estimated mutational damage through DNA mutation frequencies and RNA integrity values. Compared to UV-treated controls (C+UV), the social context of heat stress history preceding the UV assay altered keratin and cell structuring-related pathways, associated with longer embryos with over-developed pericardia displaying behavioural hypoactivity. Relative to C+UV, direct heat stress history preceding UV exposure had a hormetic effect by stimulating the cellular stress response and facilitating DNA repair, which rescued embryos from subsequent UV damage and improved their apparent fitness. However, heat stress combined with social metabolites overwhelmed embryos in the UV assay, which annihilated the hormetic effect, introduced mutations, and lowered their apparent fitness. Whilst generated in the laboratory, these findings provide an important baseline for understanding the consequences of heat stress history in natural environments, where heat stress occurs within a social context. HighlightsO_LIHeat stress had a hormetic effect against UV damage, by stimulating the heat shock response, antioxidants, and DNA repair. C_LIO_LIThe heat hormetic effect protected and/or rescued embryos from UV damage by reducing single nucleotide variants observed in RNA, lowering malformations, and accelerating development. C_LIO_LIHeat-stressed embryos released social metabolites that initiated keratin, immune, and cellular structuring responses in receivers, in turn increasing body sizes but without reducing UV-induced malformations. C_LIO_LIHeat combined with social metabolites overwhelmed embryos in response to UV, reducing fitness-relevant performance. C_LIO_LIHeat stress during early embryogenesis led to differential fitness-relevant outcomes showing a nonlinear relationship with stress intensity. C_LI Summary statementSublethal heat stress protects zebrafish embryos in a mutagenic environment, but this protective effect is lost when zebrafish embryos additionally stress each other via chemical cues. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/560724v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@a6445org.highwire.dtl.DTLVardef@3cfc64org.highwire.dtl.DTLVardef@1de41c6org.highwire.dtl.DTLVardef@b06269_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2022

Heat induces multi-omic and phenotypic stress propagation in zebrafish embryos

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the novel 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 multi-omic 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 slow-down in concert with reduced responses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolites including sulphur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signalling, glycosaminoglycan/keratan sulphate, 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 signalling. Our results prove the concept of indirect heat-induced stress propagation towards naive receivers, inducing phenotypes comparable to those resulting from direct heat exposure, but utilising distinct molecular pathways. Group-exposing a non-laboratory 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 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. Significance StatementAquatic animals utilise chemicals to mediate adaptive behaviours. For instance, predated fish release chemical cues that elicit antipredatory responses in naive receivers. But whether abiotic factors such as heat likewise alter chemical communication has received little focus. Here, we uncover a novel dimension of chemical communication -- heat-stressed donors can induce stress in naive receivers. We show that heat activates molecular stress responses, leading to the release of distinct stress metabolite classes into the environment. These stress metabolites alter the transcriptome of receivers, resulting in faster development and hypoactivity. Heat combined with stress metabolites had the largest effect, highlighting that abiotic stress, experienced both directly and indirectly, can alter chemical communication and affect embryonic development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/508176v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1e44b4borg.highwire.dtl.DTLVardef@10b6878org.highwire.dtl.DTLVardef@1f7c3bforg.highwire.dtl.DTLVardef@15436bc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe elucidate the mechanism for a novel dimension of the heat stress response -- chemical communication from heat-stressed donors that induces stress in naive receivers -- constituting a positive feedback loop C_LIO_LIRepeated heat stress induces a cellular and cortisol stress response and alters the phenotype of zebrafish embryos C_LIO_LIHeat-stressed embryos release stress metabolites enriched in lipids and sulphur-containing organo-oxygen compounds C_LIO_LIIn combination, heat and stress metabolites induced 47% distinct differentially expressed genes, with many related to organ development C_LIO_LIThese stress metabolites alter the transcriptome and induce both faster development and hypoactivity in naive receivers, a similar response to that of heat stress itself C_LI

molecular biology↗