Deciphering sex-specific miRNAs as heat-recorders in zebrafish

Abstract

In the last decade, a plethora of microRNAs (miRNAs) has been reported in a wide variety of physiological processes, including reproduction, in many aquatic organisms. However, miRNAome alterations occurred by environmental cues due to water temperature increment have not yet been elucidated. With the aim to identify epigenetic regulations mediated by miRNAs in the gonads in a climate change scenario, the animal model zebrafish (Danio rerio) were subjected to high temperatures during sex differentiation, a treatment that results in male-skewed sex ratios in the adulthood. Once the fish reached adulthood, gonads were sequenced by high-throughput technologies and a total of 23 and 1 differentially expressed miRNAs in ovaries and testes, respectively, were identified two months after the heat treatment. Most of these heat-recorder miRNAs were involved in human sex-related cancer and about 400 predicted-target genes were obtained, some with reproduction-related functions. Their synteny in the zebrafish genome was, for more than half of the predicted target genes, in the chromosomes 7, 2, 4, 3 and 11 in the ovaries, chromosome 4 being the place where the sex-associated-region (sar) is localized in wild zebrafish. Further, spatial localization in the gonads of two selected heat-recorder miRNAs (miR-122-5p and miR-146-5p) showed exclusive expression in the ovarian germ cells. The present study expands the catalog of sex-specific miRNAs and deciphers, for the first time, thermosensitive miRNAs in the zebrafish gonads that might be used as potential epimarkers to predict environmental past events.

Consequences of Cancer on ZebrafishDanio rerio: Insights into Sex Determination, Sex Ratio, and Offspring Survival

“…Indeed, regarding Experiment 1, cancer does not appear to be associated with differential sex-specific mortality at the embryonic stage, nor does it play a role in sex determination (since both phenomena would have skewed the sex-ratio). These results contrasts with numerous studies that have identified sex-specific responses in zebrafish regarding various factors (e.g., (Zhou et al 2010, Li et al 2019, Giommi et al 2022, Lin et al 2022, Park et al 2022, van Gelderen et al 2022, Zhai et al 2022, Zheng et al 2022, Zhong et al 2023)), including cancers (e.g., (Lee et al 2018, 2021, Mensah et al 2019, Montal et al 2023)). One possible explanation is that the cancer type used in our study may have too low aggressiveness, as possibly evidenced by the ability of individuals affected at the embryo stage to develop into adulthood.…”

Age estimation in fishes using epigenetic clocks: Applications to fisheries management and conservation biology

“…Although DNA methylation changes with age provides a strong foundation for the development of epigenetic clocks, consideration could perhaps be paid to other epigenetic mechanisms or modifications such as histone modifications and, specially, noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs) (van Gelderen et al, 2022). In particular, quantifying levels of miRNAs is relatively easy (Lee and Shin, 2012).…”

Identification of sex-biased miRNA markers informative of heat-past events

“…Other studies in zebrafish describing the heat stress by temperature in the gonadal miRNome revealed that miR-22b and miR-301a were altered to be fully recovered three months after the exposure (Ikert and Craig, 2020). In zebrafish females, 23 miRNAs were DE in ovaries after larval heat-treatment, among which, for example, dre-miR-726-3p was downregulated while dre-miR-724-5p was upregulated (van Gelderen et al, 2022). Interestingly, these two miRNAs were both found to be downregulated in E. sea bass testis one year after heat exposure in the present study, indicating that a conservation in the heat response among species may exist.…”

“…In the Antarctic notothenioid ( Trematomus bernacchii ), adapted to extreme climates of temperatures around −1°C, an acute heat stress was able to alter 12 miRNAs in the gills, mainly pertaining to cellular stress response (Vasadia et al, 2019). Long-term effects on the miRNome were shown in zebrafish ( Danio rerio ) (van Gelderen et al, 2022) and in Atlantic cod (Bizuayehu et al, 2015). Further, adult zebrafish exposed to high temperature for 21 days changed the miRNome with a consecutive recovery in which miRNA expressions returned to their original state (Ikert and Craig, 2020).…”

“…In the Antarctic notothenioid (Trematomus bernacchii), adapted to extreme climates of temperatures around -1C, an acute heat stress was able to alter 12 miRNAs in the gills, mainly pertaining to cellular stress response (Vasadia et al, 2019). Long-term effects on the miRNome were shown in zebrafish (Danio rerio) (van Gelderen et al, 2022) and in Atlantic cod (Bizuayehu et al, 2015).…”