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Gravity is one of the most constant environmental factors across Earth’s evolution and all organisms are adapted to it. Consequently, spatial exploration has captured the interest in studying the biological changes that physiological alterations are caused by gravity. In the last two decades, epigenetics has explained how environmental cues can alter gene functions in organisms. Although many studies addressed gravity, the underlying biological and molecular mechanisms that occur in altered gravity for those epigenetics-related mechanisms, are mostly inexistent. The present study addressed the effects of hypergravity on development, behavior, gene expression, and most importantly, on the epigenetic changes in a worldwide animal model, the zebrafish (Danio rerio). To perform hypergravity experiments, a custom-centrifuge simulating the large diameter centrifuge (100 rpm ~ 3 g) was designed and zebrafish embryos were exposed during 5 days post fertilization (dpf). Results showed a significant decrease in survival at 2 dpf but no significance in the hatching rate. Physiological and morphological alterations including fish position, movement frequency, and swimming behavior showed significant changes due to hypergravity. Epigenetic studies showed significant hypermethylation of the genome of the zebrafish larvae subjected to 5 days of hypergravity. Downregulation of the gene expression of three epigenetic-related genes (dnmt1, dnmt3, and tet1), although not significant, was further observed. Taken altogether, gravity alterations affected biological responses including epigenetics in fish, providing a valuable roadmap of the putative hazards of living beyond Earth

microRNA-210 (miRNA), a well-documented miRNA, has been implicated in a myriad of biological processes, including responses to hypoxia, angiogenesis, cell proliferation, and male infertility in humans. However, a comprehensive understanding of its functions in fish requires further investigation. This study pursued to elucidate the downstream effect of dre-miR-210-5p on primary ovarian cell culture in zebrafish (Danio rerio), an animal model. A protocol was settled down by incubations with either an miR-210 mimic or a scrambled miRNA in the isolated ovaries. RNA-sequencing analysis identified ∼6000 differentially expressed target genes revealing that downregulated genes were associated with reproduction-related pathways while immune-related pathways displayed an upregulated pattern. To identify molecular markers, predicted target genes were classified into reproduction and immune cell types. These findings underscore the existence of a profound interplay between the reproductive and immune systems, with miR-210 emerging as a pivotal player in orchestrating transcriptomic alterations within fish ovaries

La biòloga Laia Ribas és una persona molt inquieta, amb un munt de projectes a l'estació de recerca marciana. Un dels que més li agraden és CatMart, un projecte per buscar vida al desert de Utah. Ella és una de les poques investigadores al món que estudien l'impacte de la gravetat en el sistema reproductiu i immunitari dels peixos

Videos exhibiting every morphological characteristic observed in both the control and hypergravity groups of zebrafish larva

Rearing density directly impacts fish welfare, which, in turn, affects productivity in aquaculture. Previous studies have indicated that high-density rearing during sexual development in fish can induce stress, resulting in a tendency towards male-biased sex ratios in the populations. In recent years, research has defined the relevance of the interactions between the environment and epigenetics playing a key role in the final phenotype. However, the underlying epigenetic mechanisms of individuals exposed to confinement remain elucidated. By using zebrafish (Danio rerio), the DNA methylation promotor region and the gene expression patterns of six genes, namely dnmt1, cyp19a1a, dmrt1, cyp11c1, hsd17b1, and hsd11b2, involved in the DNA maintenance methylation, reproduction, and stress were assessed. Zebrafish larvae were subjected to two high-density conditions (9 and 66 fish/L) during two periods of overlapping sex differentiation of this species (7 to 18 and 18 to 45 days post-fertilization, dpf). Results showed a significant masculinization in the populations of fish subjected to high densities from 18 to 45 dpf. In adulthood, the dnmt1 gene was differentially hypomethylated in ovaries and its expression was significantly downregulated in the testes of fish exposed to high-density. Further, the cyp19a1a gene showed downregulation of gene expression in the ovaries of fish subjected to elevated density, as previously observed in other studies. We proposed dnmt1 as a potential testicular epimarker and the expression of ovarian cyp19a1a as a potential biomarker for predicting stress originated from high densities during the early stages of development. These findings highlight the importance of rearing densities by long-lasting effects in adulthood conveying cautions for stocking protocols in fish hatcheries.

Rearing density directly impacts fish welfare, which, in turn, affects productivity in aquaculture. Previous studies have indicated that high-density rearing during sexual development in fish can induce stress, resulting in a tendency towards male-biased sex ratios in the populations. In recent years, research has defined the relevance of the interactions between the environment and epigenetics playing a key role in the final phenotype. However, the underlying epigenetic mechanisms of individuals exposed to confinement remain elucidated. By using zebrafish (Danio rerio), the DNA methylation promotor region and the gene expression patterns of six genes, namely dnmt1, cyp19a1a, dmrt1, cyp11c1, hsd17b1, and hsd11b2, involved in the DNA maintenance methylation, reproduction, and stress were assessed. Zebrafish larvae were subjected to two high-density conditions (9 and 66 fish/L) during two periods of overlapping sex differentiation of this species (7 to 18 and 18 to 45 days post-fertilization, dpf). Results showed a significant masculinization in the populations of fish subjected to high densities from 18 to 45 dpf. In adulthood, the dnmt1 gene was differentially hypomethylated in ovaries and its expression was significantly downregulated in the testes of fish exposed to high-density. Further, the cyp19a1a gene showed downregulation of gene expression in the ovaries of fish subjected to elevated density, as previously observed in other studies. We proposed dnmt1 as a potential testicular epimarker and the expression of ovarian cyp19a1a as a potential biomarker for predicting stress originated from high densities during the early stages of development. These findings highlight the importance of rearing densities by long-lasting effects in adulthood conveying cautions for stocking protocols in fish hatcheries.

Hypatia I (https://hypatiamars.com) és un projecte de divulgació i ciència de nou dones catalanes, multidisciplinars, multigeneracionals i multisectorial, amb l’objectiu principal de promoure les dones i les nenes en l’àmbit de les carreres de ciència, tecnologia, enginyeria, art i matemàtiques (sigles en anglès: STEAM). La tripulació Hypatia I va estar seleccionada per a la Mars Society per conviure a una estació anàloga de Mart, la Mars Desert Research Station (MDRS), al desert de Utah (Estats Units) durant 15 dies el mes d’abril del 2023. Durant la seva estada, cadascuna de les tripulants va desenvolupar els seus propis projectes de recerca. Els àmbits en que es desenvolupen els projectes d’Hypatia I són quatre: Astronomia, Enginyeria, Biologia i Comunicació. Les Drs. Ribas i Sabaté, explicaran les seves vivències durant la simulació marciana i els seus projectes de recerca desenvolupats durant la seva missió. Aquests van des de generació de bateries usant l’orina de les tripulants per a generar energia lumínica per a créixer germinats, fins a l’aqüicultura marciana i cerca de vida marciana. Durant els dos anys des del naixement de Hypatia I, s’han creat entre totes les tripulants 30 projectes de divulgació i recerca Hypatia I s’ha fet possible gràcies a la captació econòmica de més de 36 patrocinis i col·laboracions

Una nueva tripulación de mujeres de distintas edades y perfiles protagonizará la siguiente simulación en el desierto de Utah (Estados Unidos)

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La investigadora del CSIC explora las posibilidades de la acuicultura marciana en Hypatia I, una misión de mujeres científicas en la Mars Desert Research Station

Laia Ribas, investigadora del CSIC en el Instituto de Ciencias del Mar, lleva unas dos décadas trabajando con la acuicultura sostenible. Hace tres, comenzó a interesarse por la cría de peces en Marte. Porque, ¿de qué otra forma se podría conseguir una proteína animal sencilla y llena de ácidos grasos? Ribas es una de las miembros de la misión Hypatia

[ES] Durante 15 días la expedición busca recrear cómo serían salidas extravehiculares o crear un protocolo de comunicaciones con la Tierra, [CAT] La missió Hypatia I permetrà a nou investigadores catalanes fer recerca com si fossin astronautes a Mart

La missió marciana Hypatia I al desert d'Utah compta amb la presència de nou científiques catalanes que fa temps que es preparen

Fish farms are prone to disease outbreaks and stress due to high-density rearing conditions in tanks and sea cages, adversely affecting growth, reproduction, and metabolism. To understand the molecular mechanisms affected in the gonads of breeder fish after an immune challenge, we investigated the metabolome and the transcriptome profiles in zebrafish testes after inducing an immune response. After 48 h of the immune challenge, ultra-high-performance liquid chromatography (LC-MS) and transcriptomic analysis by RNA-seq (Illumina) resulted in 20 different released metabolites and 80 differentially expressed genes. Among these, glutamine and succinic acid were the most abundant metabolites released and 27,5% of the genes belong to either the immune or reproduction systems. Pathway analysis based on metabolomic and transcriptomic crosstalk identified cad and iars genes that act simultaneously with succinate metabolite. This study deciphers interactions between reproduction and immune systems and provides a basis to improve protocols in generating more resistant broodstock

[EN] In this April's "In Depth" we talked about the Martian mission Hypatia I and how marine research can contribute to make life on the red planet possible, [ES] En el “A fondo” de este mes de abril os hablamos la misión marciana Hypatia I y de cómo la investigación marina puede contribuir a hacer posible la vida en el planeta rojo, [CAT] A l’”A fons” d’aquest mes d’abril us parlem de la missió marciana Hypatia I i de com la recerca marina pot contribuir a fer possible la vida al planeta vermell

This session is part of the ICM Support Programme "The ERC journey" and intended to help ICM researchers become more familiar with the ERC grants within marine sciences. During the session key information will be provided by the national experts and complemented with tips and best practices from PIs that have already prepared an ERC proposal

The low representation of women (~33%) in Science, Technology, Engineering, Arts and Mathematics (STEAM) careers are highly concerning and cultivate male-dominant cultures across various academic and professional disciplines. This social disequilibrium is extreme in the international space sector, where women represent less than ~20% of the workforce. The Hypatia I mission —a multi-generational and multi-disciplinary crew of 9 Catalan female scientists— seeks to help address this problem. In April 2023, the Hypatia I crew will participate in a two-week Martian analog mission at the Mars Desert Research Station (MDRS, Utah, United States) with the goals of (i) performing high-quality space-related research in a simulation environment, (ii) conducting outreach and science communication activities, and most importantly, (iii) promoting female role models in STEAM-related fields and inspiring future generations of scientists, particularly young girls interested in space careers. Hypatia I works in four areas: astronomy, engineering, space-biology, and communication. In particular, biological-related experiments will be presented. First, by studying the developmental alterations of zebrafish (Danio rerio), a well-known animal model subjected to hypergravity conditions. Second, by analyzing DNA epigenetic changes by using a portable DNA sequencer. Further, outreach activities will be exposed. The crew members of Hypatia I aims to inspire and promote females and girls in STEAM careers and wish that many more Hypatia’s II, III, IV…will be created giving visibility to the relevance of women in science

The sex ratio is a key ecological demographic parameter crucial for population viability. However, the epigenetic mechanisms operating during gonadal development regulating gene expression and the sex ratio remain poorly understood. Moreover, there is interest in the development of epigenetic markers associated with a particular phenotype or as sentinels of environmental effects. Here, we profiled DNA methylation and gene expression of 10 key genes related to sex development and stress, including steroidogenic enzymes, and growth and transcription factors. We provide novel information on the sex-related differences and on the influence of elevated temperature on these genes in zebrafish, a species with mixed genetic and environmental influences on sex ratios. We identified both positive (e.g., amh, cyp11c and hsd11b2) and negative (e.g., cyp11a1 and dmrt1) correlations in unexposed males, and negative correlation (amh) in exposed females between DNA methylation and gene expression levels. Further, we combined DNA methylation analysis with machine learning procedures and found a series of informative CpGs capable not only of correctly identifying sex (based on cyp19a1a DNA methylation levels) but also of identifying whether males and females had been exposed to abnormally elevated temperature when young (based on amh and foxl2a DNA methylation levels, respectively). This was achieved in the absence of conspicuous morphological alterations of the gonads. These DNA methylation-based epigenetic biomarkers represent molecular resources that can correctly recapitulate past thermal history and pave the way for similar findings in other species to assess potential ecological effects of environmental disturbances in the context of climate change

L’abril del 2023 un equip de recerca de lideratge completament femení aterrarà al ‘Mars Desert Research Station’ dels EUA. La missió Hypatia I permetrà a nou científiques catalanes fer experiments de diverses disciplines acadèmiques a un ambient que recrea les condicions del planeta Mart. Laia Ribas, doctora en Biologia i investigadora principal de l’Institut de Ciències del Mar, ens explica tot el que hi ha darrere d’aquest projecte pioner

[Background] Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS., [Methods] We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume., [Results] In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance., [Discussion] BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.

Desenvolupa diferents situacions d’aprenentatge STEAM de la mà de la tripulació Hypatia I. Desenvolupa diferents situacions d’aprenentatge STEAM de la mà de la tripulació Hypatia I. Objectius: Hypatia I és una tripulació composta per nou dones científiques catalanes, amb diferents edats i experiència, que viatjarà l’abril del 2023 a l’estació anàloga de Mart situada al desert d’Utah, als Estats Units. Elles són qui han elaborat una seqüència de materials i activitats adaptades als tres cicles de l’educació primària que permeten treballar, a partir de l’aprenentatge basat en problemes de tipus STEAM, conceptes relacionats amb l’astronomia, l’enginyeria, la salut, la comunicació i la biologia. Per tant, aquest curs té un primer objectiu que és el de fer arribar el coneixement científic de la mà de dones professionals en els diferents àmbits. I ho fan a través de situacions relacionades amb el cosmos, la tecnologia espacial, la vida en condicions de gravetat zero i les aportacions científiques de les missions espacials es proposen activitats pràctiques sobre: - El càlcul de les distàncies en el sistema solar - L’elaboració d’un sistema de reciclatge d’aigua - L’extracció de l’ADN del plàtan - L’elaboració d’un menú energètic i saludable - L’elaboració d’un pòster científic Es tracta d’un recurs educatiu que treballa propostes d’aprenentatge actives i vivencials, que segueixen el model d’ensenyament 5E (Engage, Explore, Explain, Elaborate and Evaluate). A més, les activitats proposades ja les han posat en pràctica 300 infants que van guanyar una beca d’Abacus per fer aquest curs en línia des de casa durant la primavera del 2022, curs que va comptar amb un gran èxit de participació. A la part final d’aquest vídeo pots veure algunes escenes de l’acte de cloenda del curs, un acte que es va fer en el marc dels tallers infantils STEAM del festival Fixing the Future. A qui s’adreça?: El curs s’ofereix al professorat de primària, tot i que també pot ser adequat per als primers

[ES] En el juego de cartas Hypatia I formarás parte de la tripulación de Astronautas para conseguir todas las misiones, [CAT] Al joc de cartes Hypatia I formaràs part de la tripulació d’Astronautes per aconseguir totes les missions

The transcriptomic analysis is crucial to understanding the functional elements of the genome. The classic method is screening for differentially expressed genes (DEGs). Since 2005 weighted gene co-expression network analysis (WGCNA) has emerged as a powerful method to explore the relationships between genes. However, a method combining the two, i.e., filtering the transcriptome dataset by DEGs or other criteria and then applying WGCNA (DEGs+WGCNA), has become common. This is of concern because it can the resulting underlying architecture of the network and lead to wrong conclusions. Here, we explore a plot twist to transcriptome data analysis: combining WGCNA, exploiting the whole dataset and not affecting the topology of the network, with the strength and relative simplicity of DEGs analysis (WGCNA+DEGs). We tested WGCNA+DEGs against DEGs+WGCNA to publicly available transcriptomic data in one of the most transcriptomically complex tissues and delicate process: vertebrate gonads undergoing sex differentiation. We generalized our results in three systems: sea bass, mouse, and human. Despite the diversity of sex-determining systems in vertebrates, a common feature is that a complex network of multiple regulatory interactions of genes associated with male and female pathways are expressed simultaneously as opposing forces. Although the gene networks involved in converting the gonads into ovaries or testis are relatively conserved during sex differentiation, the temporal and relative expression, as well as the relative position within the network, are different across vertebrates. The use of network properties and tools could contribute to better resolve such complex networks. As a result, WGCNA+DEGs clearly outperformed DEGs+WGCNA. First, the networks model fit, node connectivity measures as well as other network statistics improved, the number of modules and key genes retained increased and, importantly, the GO terms of biological processes provided a more meaningful

All forms of life on our planet have been formed under a common factor, gravity; for which it is easy to deduce that any change in this constant could trigger important alterations in these forms of life in the near future settlements beyond Earth. Although some studies use altered gravity to evaluate different animal and cellular models and systems, including fish models, almost nonexistent data regarding molecular mechanisms in fish are found. This work aims to understand the effects of hypergravity on gene expression and epigenetics in zebrafish during early stages of development. We designed a centrifuge by adding two arms with gondolas to place zebrafish larvae at a force of 3 gravities during 6 days post fertilization (dpf). The survival and hatching rate were measured daily, and while no significant changes were found in hatching rate, survival of larvae were decreased up to 20%. The gene expression and global DNA methylation were evaluated in larvae at the end of the treatment, and we found over-expression on some evaluated genes, and a significant global DNA hypermethylation in the larvae exposed to hypergravity. Taken together, these findings show how alterations of Earth-gravity could affect some basic biological responses in fish, and thus being the first steps in exploring molecular events in cultured fish in space-related environments.

The low representation of women (~33%) in Science, Technology, Engineering and Mathematics (STEM) careers is extremely concerning and cultivates male-dominant cultures across a variety of academic and professional disciplines. In Spain, only 39% of national projects are led by women, thus evidencing the so-called “leaking pipeline”, that is, the tendency of women and other underrepresented groups to eventually abandon STEM-related fields. This social disequilibrium is particularly strong in the international space sector, where women represent less than ~20% of the workforce. The Hypatia I mission —a multi-generational and multi-disciplinary crew of 9 female scientists— seeks to help address this problem. In April 2023, the Hypatia I crew will participate in a two-week Martian analog mission at the Mars Desert Research Station (Utah, United States) with the goal of (i) performing high-quality space-related research in a simulation environment, (ii) conducting outreach and science communication activities, and most importantly, (iii) promoting female role models in STEM-related fields and inspiring future generations of scientists, particularly young girls interested in space careers

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

Hypatia I, un projecte per enlairar vocacions científiques.

És investigadora a l’Institut de Ciències del Mar (ICM-CSIC) a Barcelona, l’institut de recerca marina de més prestigi de l’Estat, on fa recerca en el camp de l’aqüicultura (les granges de peix). També és professora associada a la Universitat Autònoma de Barcelona (UAB). Doctorada en ciències biològiques, la seva tesi es va centrar en l’estudi de l’estrès i les respostes immunes dels peixos per desenvolupar marcadors que milloressin la producció aqüícola. Va aprendre eines genòmiques, cosa que li va permetre obtenir un postdoctorat al Regne Unit per estudiar la resposta immune dels amfibis a les infeccions fúngiques. Està especialitzada en l’estudi dels efectes ambientals en el desenvolupament dels òrgans reproductors dels peixos

Sex ratio depends on sex determination mechanisms and is a key demographic parameter determining population viability and resilience to natural and anthropogenic stressors. There is increasing evidence that the environment can alter sex ratio even in genetically sex-determined species (GSD), as elevated temperature can cause female-to-male sex reversal (neomales). Alarmingly, neomales are being discovered in natural populations of several fish, amphibian and reptile species worldwide. Understanding the basis of neomale development is important for conservation biology. Among GSD species, it is unknown whether those with chromosomal sex determination (CSD), the most common system, will better resist the influence of high temperature than those with polygenic sex determination (PSD). Here, we compared the effects of elevated temperature in two wild zebrafish strains, Nadia (NA) and Ekkwill (EKW), which have CSD with a ZZ/ZW system, against the AB laboratory strain, which has PSD. First, we uncovered novel sex genotypes and the results showed that, at control temperature, the masculinization rate roughly doubled with the addition of each Z chromosome, while some ZW and WW fish of the wild strains became neomales. Surprisingly, we found that at elevated temperatures WW fish were just as likely as ZW fish to become neomales and that all strains were equally susceptible to masculinization. These results demonstrate that the Z chromosome is not essential for male development and that the dose of W buffers masculinization at the control temperature but not at elevated temperature. Furthermore, at the elevated temperature the testes of neomales, but not of normal males, contained more spermatozoa than at the control temperature. Our results show in an unprecedented way that, in a global warming scenario, CSD species may not necessarily be better protected against the masculinizing effect of elevated temperature than PSD species, and reveal genotype-by-temperature interaction

All living organisms that inhabit Earth have evolved under a common value of gravity, which amounts to an acceleration of 9.81 m/s2 at mean sea level. Changes on it could cause important alterations that affect vital biological functions. The crescent interest in spatial exploration has opened the question of how exactly these changes in gravity would affect Earth life forms on space environments. This work is the result of a collaborative co-supervision of a master thesis between experts in the area of space sciences and biology, and it can serve as a case study for training experts in such interdisciplinary environments. In particular, we focus on the effect of gravity as a pressure factor in the development of zebrafish (Danio rerio) in the larval stage as a model organism using up-to-date (genomic and epigenetic) techniques. Given the high cost of any experiment in true low gravity (which would require a space launch), we performed an initial experiment in hypergravity to develop the methodologies and identify good (epi)genetic markers of the effect of gravity in our model organism. Previous studies in zebrafish have shown how alteration in gravity effects the development and the gene expression of important regulatory genes. For this study, we firstly customized a small laboratory scale centrifuge to study changes in fish physiology together with changes at molecular levels. We exposed zebrafish larvae from 0 to 6 days post fertilization to the simulated hypergravity (SHG) (100 rpm  3g). After 6 days of hypergravity exposition the larvae showed changes in their swimming and flotation patterns, and presented corporal alterations. Then, we assessed gene expression of genes implicated in important biological processes, (e.g., epigenetics), and an upregulation were observed when compared to the control. Taken together, these preliminary findings show how gravity alterations could affect some basic biological responses, and illustrate the potential of developing ne

La matemàtica Ariadna Farrés i la biològa Laia Ribas ens presenten el projecte Hypatia, que vol simular la vida a Mart en un complex situat al desert de Utah, als Estats Units