Consequences of Cancer on Zebrafish Danio rerio: Insights Into Sex Determination, Sex Ratio, and Offspring Survival

Authors: Justine Boutry, Mathieu Douhard, Klara Asselin, Antoine M. Dujon, Jordan Meliani, Olivier De Backer, Delphine Nicolas, Aaron G. Schultz, Peter A. Biro, Christa Beckmann, Laura Fontenille, Karima Kissa, Beata Ujvari, Frédéric Thomas

Source: Ecology And Evolution (Aug 2025)

Abstract

Offspring sex ratio has been proposed as an indicator of the risk of developing certain cancers in humans, but offspring sex ratio may also be a consequence of the disease.

In this study, we investigate this subject using the zebrafish, Danio rerio, as a model system. First, we explore whether inducing skin cancer at an early stage of the host’s life (embryonic stage) has the potential to influence sex determination and/or sex-specific mortality. Second, we investigate whether the sex ratio in offspring produced by tumor-bearing adult females differs from that of healthy females. Third, we compare the survival (until sexual maturity) of offspring produced by cancerous and non-cancerous females.

We found that skin cancer did not influence sex determination and the sex ratio of the offspring. However, consistent with previous studies on other model systems, the survival of offspring was higher when mothers were cancerous, suggesting that diseased females allocate more resources to current reproductive effort compared to their healthy counterparts.

This study makes a significant contribution to our understanding of the ecological and evolutionary consequences of host-tumor interactions in animals.

Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates

Authors: Antoine M. Dujon; Peter A. Biro; Beata Ujvari; Frédéric Thomas

Source: Royal Society Open Science (Jul 2025)

Abstract

The multistage carcinogenesis model predicts that cancer risk should increase with body size and longevity owing to greater cell numbers and divisions, which provide more opportunities for mutations. However, the perceived lack of such associations across species, named ‘Peto’s paradox’, suggests that larger or longer-lived animals may have evolved enhanced cancer suppression mechanisms.

Empirical tests of this paradox have been limited by data availability, but large-scale zoo datasets now enable comparative analyses of cancer prevalence in vertebrates. Currently used statistical methods, however, often fail to adequately account for uncertainty in key model parameters.

In this study, we use Bayesian methods to reanalyse these datasets and explore Peto’s paradox, emphasizing the importance of quantifying uncertainty in comparative oncology. Our results show that body mass is positively associated with malignancy risk in mammals and amphibians, while it is negatively associated with cancer mortality in mammals. Longevity is positively associated with malignancy risk in non-avian sauropsids and amphibians. However, these relationships are accompanied by effect sizes with substantial uncertainty, primarily owing to small sample sizes.

Through simulations, we demonstrate the limitations of current datasets and models. We also discuss the broader implications of Peto’s paradox and suggest recommendations for improving future research on cancer risk across species.

Is malathion oncogenic for mosquitoes? A transcriptomic and histological study of adults derived from malathion exposed larvae

Authors: Audrey Arnal, Erika Burioli, Lisa Jacquin, Sophie Labrut, Stéphane Duchon, Marie Rossignol, Delphine Nicolas, Beata Ujvari, Antoine Dujon, Jordan Meliani, Jérôme Abadie, Frédéric Thomas, Vincent Corbel

Source: Ecotoxicology and Environmental Safety (Aug 2025)

Abstract

Malathion is a widely used pesticide with potentially oncogenic properties and may have deleterious effects on organism health and fitness. Although malathion use is now restricted in the European Union, it remains widely used for public health campaigns in other parts of the world, particularly for mosquito control. Understanding its sublethal and long-term effects is thus essential, both for evaluating its ecotoxicological impacts and for anticipating resistance mechanisms. However, empiric data on its effects in wild organisms – especially in invertebrates – remain limited.

Here, we quantitatively investigated whether larval exposure to environmentally realistic concentrations of malathion could affect mosquito tissue structure and gene expression profiles of adult Aedes aegypti (yellow fever mosquitoes), using both RNA-seq and histological approaches.

Results show no neoplastic or pre-neoplastic lesions in adults exposed to malathion during larval development, contrary to previous studies in other organisms showing carcinogenic effects of malathion. However, our differential gene expression analyses revealed significant changes in genes related to mitochondrial function, energy metabolism, and detoxification pathways, suggesting significant physiological impacts of malathion in adults after early-life pesticide exposure.

Notably, females exhibited stronger transcriptomic responses than males, including the upregulation of genes involved in detoxification (e.g., P450 cytochromes), olfactory perception, and stress response, with potential consequences for resistance mechanisms.

Our findings underscore the ability of mosquitoes to mount transient molecular responses to environmental pollutants, potentially contributing to the long-term selection of metabolic resistance traits – an outcome with important implications for vector control strategies.

Ecology of vertical tumor transmission in the freshwater cnidarian Hydra oligactis

Authors: N. Stepanskyy, M. Pascal, K. Asselin, L. Brazier, J. Meliani, S. Tissot, A. M. Nedelcu, J. Tökölyi, B. Ujvari, F. Thomas & A. M. Dujon

Source: Scientific Reports (Feb 2025)

Abstract

Transmissible tumors are increasingly regarded as a new form of parasitic life, but relatively little is known about the ecology and evolution of their interactions with their host. In this work, we provide new insights into transmission dynamics of vertically transmitted tumors in the freshwater cnidarian Hydra oligactis.

First, we found tumoral hydra to be infectious at any age, regardless of whether they were in their asymptomatic or symptomatic phases, with the bacteriome composition remaining constant during both phases. Interestingly, tumor transmission increased with the number of tentacles, particularly for hydras with supernumerary tentacles.

Additionally, tumors developed earlier in the offspring from parents with more advanced tumors. Furthermore, despite being direct descendants of tumoral polyps, some hydras never developed tumoral phenotype. The latter exhibited a distinct bacteriome composition, reduced lifespan and a lower tentacle number increase over time. Interestingly, the tumor phenotype expression in these hydras appears to be able to skip generations, as transmission occurred at any age from parents to offspring.

We discuss these results in the context of current knowledge on the evolutionary ecology of host-transmissible tumor interactions as well as parasite-host interactions and suggest avenues for further research.

Adaptive divergence in diets between the sexes in a tropical snake (Stegonotus australis, Colubridae)

Authors: Gregory P Brown, Thomas Madsen & Richard Shine

Source: Oecologia (Mar 2025)

Abstract

Males and females within a population may differ in dietary composition either as a non-adaptive consequence of sexual dimorphism, or because specific food types enhance fitness more in one sex than the other. To test between those two explanations, we can ask whether the consumption of a food type (a) is constrained by sexually dimorphic traits such as body size, or (b) differentially benefits the sex that consumes that food more frequently.

A 23-year field study of Slatey-Grey Snakes (Stegonotus australis) in tropical Australia provided data on 663 meals, of which 130 were reptile eggs (primarily from Keelback Snakes (Tropidonophis mairii)).

Over the same range of snake SVLs, eggs were consumed more often by female than by male Slatey-Grey Snakes (25.8 versus 15.2% of records), but consumption of reptile eggs was independent of snake body size. Female Slatey-Grey Snakes were not more common or more active than males during Keelback nesting periods, but they were more likely to be captured in the vicinity of Keelback oviposition sites than were males. In years with higher availability of Keelback eggs, female Slatey-Grey Snakes had higher clutch sizes and clutch masses (plausibly reflecting the nutritional benefits of eating reptile eggs to provision reptile eggs).

In combination, our results suggest an adaptive basis to the sex-based divergence in dietary composition in Slatey-Grey Snakes.

First evidence for the evolution of host manipulation by tumors during the long-term vertical transmission of tumor cells in Hydra oligactis

Authors: Justine Boutry, Océane Rieu, Lena Guimard, Jordan Meliani, Aurora M Nedelcu, Sophie Tissot, Nikita Stepanskyy, Beata Ujvari, Rodrigo Hamede, Antoine M Dujon, Jácint Tökölyi & Frédéric Thomas

Source: eLife (Mar 2025)

Abstract

While host phenotypic manipulation by parasites is a widespread phenomenon, whether tumors – which can be likened to parasite entities, can also manipulate their hosts is not known. Theory predicts that this should nevertheless be the case, especially when tumors (neoplasms) are transmissible.

We explored this hypothesis in a cnidarian Hydra model system, in which spontaneous tumors can occur in the lab, and lineages in which such neoplastic cells are vertically transmitted (through host budding) have been maintained for over 15 years. Remarkably, the hydras with long-term transmissible tumors show an unexpected increase in the number of their tentacles, allowing for the possibility that these neoplastic cells can manipulate the host.

By experimentally transplanting healthy as well as neoplastic tissues derived from both recent and long-term transmissible tumors, we found that only the long-term transmissible tumors were able to trigger the growth of additional tentacles. Also, supernumerary tentacles, by permitting higher foraging efficiency for the host, were associated with an increased budding rate, thereby favoring the vertical transmission of tumors.

To our knowledge, this is the first evidence that, like true parasites, transmissible tumors can evolve strategies to manipulate the phenotype of their host.

𝐅𝐫𝐨𝐦 𝐓𝐚𝐬𝐦𝐚𝐧𝐢𝐚𝐧 𝐃𝐞𝐯𝐢𝐥𝐬 𝐭𝐨 𝐇𝐮𝐦𝐚𝐧 𝐇𝐨𝐩𝐞: 𝐁𝐞𝐚𝐭𝐚 𝐔𝐣𝐯𝐚𝐫𝐢’𝐬 𝐌𝐢𝐬𝐬𝐢𝐨𝐧 𝐀𝐠𝐚𝐢𝐧𝐬𝐭 𝐂𝐚𝐧𝐜𝐞𝐫

Click HERE to access the LinkedIn post and the video

Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum

Authors: Mitchell L. Trickey, Mrittika Chowdury, Georgina Bramwell, Natalie A. Counihan & Tania F. de Koning-Ward

Source: Journal of Biomedical Science (Feb 2025)

Abstract

Background
Malaria parasites establish new permeation pathways (NPPs) at the red blood cell membrane to facilitate the transport of essential nutrients from the blood plasma into the infected host cell. The NPPs are critical to parasite survival and, therefore, in the pursuit of novel therapeutics are an attractive drug target. The NPPs of the human parasite, P. falciparum, have been linked to the RhopH complex, with the monoallelic paralogues clag3.1 and clag3.2 encoding the protein RhopH1/CLAG3 that likely forms the NPP channel-forming component. Yet curiously, the combined knockout of both clag3 genes does not completely eliminate NPP function. The essentiality of the clag3 genes is, however, complicated by three additional clag paralogs (clag2, clag8 and clag9) in P. falciparum that could also be contributing to NPP formation.

Methods
Here, the rodent malaria species, P. berghei, was utilised to investigate clag essentiality since it contains only two clag genes, clagX and clag9. Allelic replacement of the regions encompassing the functional components of P. berghei clagX with either P. berghei clag9 or P. falciparum clag3.1 examined the relationship between the two P. berghei clag genes as well as functional orthology across the two species. An inducible P. berghei clagX knockout was created to examine the essentiality of the clag3 ortholog to both survival and NPP functionality.

Results
It was revealed P. berghei CLAGX and CLAG9, which belong to two distinct phylogenetic clades, have separate non-complementary functions, and that clagX is the functional orthologue of P. falciparum clag3. The inducible clagX knockout in conjunction with a guanidinium chloride induced-haemolysis assay to assess NPP function provided the first evidence of CLAG essentiality to Plasmodium survival and NPP function in an in vivo model of infection.

Conclusions
This work provides valuable insight regarding the essentiality of the RhopH1 clag genes to the NPPs functionality and validates the continued investigation of the RhopH complex as a therapeutic target to treat malaria infections.

The Importance of Addressing Evolutionary Mismatches in the Production Management of Aquaculture Species

Authors: Thomas S. Mock, Davis S. Francis, Antoine M Dujon

Source: Reviews in Aquaculture (Nov 2024)

Abstract

To achieve production goals, aquaculture often modifies the environments of farmed species, creating conditions that differ significantly from their natural habitats. These alterations can result in evolutionary mismatches, where traits that evolved to optimise survival and reproduction in the wild become maladaptive in farming settings. This can lead to a conflict between traits desired for farming and those favoured by natural selection.

In this opinion piece, we examine cases where such evolutionary mismatches arise, their impact on production, and strategies to mitigate these effects. We provide examples of species and farming practices that have been optimised through selective breeding and evolutionary studies and highlight practical solutions that can be applied to the many aquaculture species for which farming practices remain suboptimal.

Additionally, we suggest directions for future research to deepen our understanding of evolutionary mismatches in aquaculture.

Beyond Peto’s paradox: expanding the study of cancer resistance across species

Authors: Antoine M Dujon, Amy M Boddy, Rodrigo Hamede, Beata Ujvari, Frédéric Thomas

Source: Evolution (Nov 2024)

Abstract

Peto’s paradox, which highlights the lower-than-expected cancer rates in larger and/or longer-lived species, is a cornerstone of discussions at the intersection of ecology, evolution, and cancer research. It prompts investigations into how species with traits that theoretically increase cancer risk manage to exhibit cancer resistance, with the ultimate goal of uncovering novel therapies for humans.

Building on these foundational insights, we propose expanding the research focus to species that, despite possessing traits beyond size and longevity that theoretically increase their cancer risk, exhibit unexpected cancer resistance.

Testing Peto’s paradox without interference from transient dynamics also requires considering species that are at an equilibrium between cancer risks and defenses, which is increasingly challenging due to anthropogenic activities. Additionally, we argue that transmissible cancers could significantly help in understanding how the metastatic process might be naturally suppressed.

This research perspective is timely and aims to support the continued and in-depth identification of anti-cancer adaptations retained throughout evolution in the animal kingdom.