Urban Environments, Stress and Its Biomarkers
Tadeáš Dvořák

Urban stress is a bodily and mental response to stimulation in urban environments. We can measure this response using cardiorespiratory or neurophysiological methods and observe changes in heart rate variability, brain activity and other biomarkers. Few studies have investigated what environmental parameters drive urban stress. We aim to establish if the underlying geometry of urban spaces and its metabolic demands on the visual system contribute to urban stress. In a set of real-world and laboratory experiments, participants will be exposed to built and green spaces with different low-level geometric parameters. Findings could reveal geometric patterns that reduce stress, contributing to healthier urban environments.

Characterising the link between indoor air, dust and textile contamination
Özge Edebali 

The doctoral thesis aims to investigate the entry of aromatic amines (AAs) into water bodies from indoor environments and to characterize the link between indoor air, dust, and textiles. AAs are emitted from various indoor sources and can sorb from textiles, which can release the chemicals during laundering and discharge them into water systems. The thesis will characterize the emissions of AAs to indoor air and dust levels and their uptake from indoor air to textiles. Samples of air and dust will be taken from the hairdresser’s salon, smoking pubs and houses, restaurant kitchens, and non-smoking houses. Textiles will also be used as a passive air sampler.

Proteins are often exposed to harsh and unnatural conditions in industrial applications, making it necessary to modify their properties. Protein engineering can enhance protein performance and make them more suitable for industrial use, with unsupervised machine learning enabling the use of a large amount of unannotated biological data. Latent space-based models, such as variational autoencoders (VAEs), map input proteins into internal coordinate space, and the structure of this latent space can thus reveal their meaningful representations. This information can be used to guide the search space in rational protein design by suggesting new protein sequences or identifying important residues for mutations.

Protein Engineering of Staphylokinase with Improved Thrombolysis
Jan Mičan

Staphylokinase is an easy-to-produce protein that offers a way to treat blood clot-caused diseases such as ischemic stroke. In this study, we performed computational design of staphylokinase's protein-protein interface with plasmin to improve its affinity to plasmin and efficiency. We selected four mutants (SAK01-04) for experimental characterization. SAK01 has shown sixfold higher plasmin affinity and nine times higher selectivity than wild-type staphylokinase. SAK01 also has slightly higher fibrinolytic effectivity. SAK01 has proved that computational design can improve staphylokinase's affinity to plasmin and translate to better thrombolytic efficiency. Prospectively, we aim to create improved mutants using rational design and other methods.

Microbiome and pharmacotherapy in patients with gastrointestinal disorders
Natálie Mlčůchová 

Background: Etiopathogenesis of gastrointestinal disorders (GDs), such as gastroesophageal reflux disease (GERD) and its complications, pancreatic cancer (PANC), and colorectal adenocarcinoma (CRC) is multifactorial; risk factors for disease development and/or progression include external factors, dysbiosis of host microbiota, genetic predisposition, and responsiveness to therapy.
Objectives: The main aim of the dissertation project is to identify potential markers at the level of the host microbiome.
Methods: Human and microbial DNA will be isolated from blood and biopsies from the digestive tract. Microbial DNA will be analyzed by 16S rRNA amplicon sequencing and quantified by multiplex qPCR method.
Outcomes: Paired comparison of bacteriomes between healthy and pathological parts of the digestive tract will be performed to identify potentially risky host bacteriome profiles.
Acknowledgements: This project is supported by the Ministry of Health of the Czech Republic, grant Nr. NU20-03-00126.

Automated functional metabolomics and application to case-control disease studies
Hana Seličová

Staphylokinase is an easy-to-produce protein that offers a way to treat blood clot-caused diseases such as ischemic stroke. In this study, we performed computational design of staphylokinase's protein-protein interface with plasmin to improve its affinity to plasmin and efficiency. We selected four mutants (SAK01-04) for experimental characterization. SAK01 has shown sixfold higher plasmin affinity and nine times higher selectivity than wild-type staphylokinase. SAK01 also has slightly higher fibrinolytic effectivity. SAK01 has proved that computational design can improve staphylokinase's affinity to plasmin and translate to better thrombolytic efficiency. Prospectively, we aim to create improved mutants using rational design and other methods.

ApoE, an enigmatic cellular player in neurodegeneration
Aneta Vašková

Apolipoprotein E (ApoE) is a 299-residue glycoprotein that plays an enigmatic role in neurodegeneration. It can undergo fragmentation and forms insoluble aggregates (especially ApoE4 isoform), which are a major hallmark of the neurodegenerative process. ApoE fragments are capable of overcoming the nuclear membrane and translocating to the cell nucleus. Surprisingly, the N-terminal domain of ApoE is able to interact with DNA. In this project, we aim to decipher a mode of molecular recognition of double-stranded DNA by ApoE fragments, and its cellular consequences. To do this, we employ protein biochemistry and structural biology techniques to reconstitute and visualize ApoE-DNA complexes. Complementary, we will use cell-based assays to probe the transcription-deregulation activity of ApoE proteins and its prevention through small-molecule modulators.

Deciphering the human prenatal chemical exposome using high-resolution mass spectrometry and placenta
Thomas Contini

Exposure of the population to complex mixtures of xenobiotics is suspected of contributing to many adverse health outcomes, including chronic diseases that are the major causes of premature death worldwide. Many chronic diseases may have their origins in utero. Therefore, it is essential to focus on one of the most critical and vulnerable periods of development, i.e., the prenatal period.

The placenta, a part of the fetoplacental unit, is a promising matrix to study exposure of the fetus to xenobiotic mixtures during pregnancy but remains underexplored for exposure assessment. Metabolomic profiling of placenta extracts using high-resolution mass spectrometry (HRMS) would enable the simultaneous characterization of accumulating exogenous chemicals and identification of associated perturbations in biochemical signaling pathways. However, the placenta is a large organ with tissues of different origins and the spatial distribution of exogenous chemicals remains unknown. Furthermore, there is currently no standardized method for sampling placenta.

The main objective of this project is to study intra- and inter-variability of chemical distribution in placenta using HRMS-based methodologies in order to develop a standardized sampling protocol for future large-scale applications in mother-child cohorts. The second aim of is to generate a comprehensive annotation of the internal chemical exposome and metabolome of human placenta. Placenta samples will be collected (n=25, same from boys and girls), and an analytical workflow based on liquid and gas chromatography (LC & GC) coupled to HRMS used to provide wide and complementary coverage of the chemical space.

This study investigated the exposure levels of per- and polyfluorinated alkyl substances (PFAS) in professional firefighters, freshly recruited firefighters, and a control group. The study aimed to determine whether PFAS impair thyroid hormone homeostasis and whether the associations between PFAS and thyroid hormones are modulated by iodine deficiency. The findings suggest a potential relationship between serum levels of PFAS and thyroid hormones in the three different groups, indicating that exposure to PFAS may be associated with disruptions in thyroid function. To our knowledge, this is the first study to investigate the associations among an extended list of PFAS, thyroid hormones, and iodine concentration in a group of differently PFAS-exposed males.

The explanation of educational disparities in adiposity by lifestlyle socioeconomic and mental health mediators
Anna Bartošková

Background: The inverse association between education and obesity is well-known. However, education level per se is not directly related to obesity. Therefore, this study aims to assess diverse mediators in the educational disparities in adiposity.
Methods: In total, 2154 participants aged 25-64 years. Adiposity assessment was based on 4 adiposity biomarkers. The mediation potential of 8 factors was assessed in the multiple mediation model.
Results: In women, the negative indirect effect was significant via dietary risk, alcohol intake, income, and mental health. In both sexes, we observed a positive significant indirect effect via sedentary behaviours, suggesting that sedentary behaviours reduce the protective potential of higher educational levels on adiposity.

Reproducible and scalable annotation of fragmentation spectra using the matchms Galaxy tools ecosystem
Helge Hecht

Annotation of spectra with a chemical identity is considered as one of the bottlenecks in mass spectrometry-based omics disciplines. Compound identity can be assigned based on scores from matching experimentally acquired spectra to references in a spectral library. The matchms python library has fostered the development of a larger ecosystem of connected tools focusing on matching of fragmentation spectra for compound identification. This includes machine learning based scores such as Spec2Vec and MS2DeepScore as well as other means of compound identification, such as molecular networking or analog search (MS2Query). We are taking the functionalities of matchms – spectral matching, molecular networking, and spectral library processing to the cloud with the matchms Galaxy tool suite for reproducible and scalable compound identification

Maternal Prenatal Vitamin B12 Intake and Child Cognitive Development
Hrežová Eliška

The association between prenatal vitamin B12 intake and cognitive functioning in children is unclear. We examined such association in Czech part of European Longitudinal Study of Pregnancy and Childhood. Dietary data was measured using food frequency questionnaire. Parents reported on their child´s speech and language development at 18 months, 3, 5, and 7 years of age. Intelligence Quotient (IQ) was measured at the individual examination of children at 8 years. Data were analysed using multiple linear and logistic regression models. Children of mothers with higher B12 intake scored better in speech and language tests and had higher IQ than children of mothers with lower B12 intake in fully adjusted models.

Investigation of emerging aquatic contaminants emissions in municipal wastewaters using passive sampling
Simona Krupčíková

My project aims to develop a method for monitoring aromatic amines (AAs) in wastewaters and recipient surface water using passive sampling. The design of passive sampler (PS) is based on a combination of a suitable adsorbent and a diffusive hydrogel layer.
The diffusion of AAs through 1.5% agarose hydrogel is characterized by gel stacking method at the different pH values regarding the pH-dependent dissociation of AAs.
Solid phase extraction method for water samples analysis is developed and optimized using Empore disks SDB-RPS as a sorbent. Nine out of twenty AAs were detected. Using Empore disks SDB-RPS based PS, more AAs (fifteen) are detected in screening at the wastewater treatment plant in Modřice.

Supramolecular solvent-based extraction method for the determination of a wide-range of legacy and emerging environmental contaminants in indoor dust
Paula Marcineková 

Indoor environments are burdened with synthetic chemicals. These chemicals are detected in both gas and particulate phase of the indoor environments and humans are exposed to them constantly. We have a good knowledge of some chemical pollutants that are typically detected in indoor dust; however, less is known about emerging contaminants. The objective of our study was to develop an efficient supramolecular solvent (SUPRAS) extraction method suitable for extraction of wide range of chemical pollutants in house dust. Seven different mixtures of SUPRAS were investigated for extraction efficiency for a broad range of chemicals of interest. LC-MS and GC-MS were used for detection of the targeted chemical classes. The results show recoveries for the more volatile compounds at 40-60 %, while the less volatile compounds reach up to 90 % recovery. A great advantage of the use of SUPRAS is its ability to extract different polarity compounds simultaneously while keeping very low SUPRAS to sample ratio. SUPRAS extracts can be used in suspect screening and non-target analysis. This allows for detection of an even broader range of chemicals, potentially exposing many new and unknown pollutants in the indoor environment.

Pull-down assay as a novel approach for the identification of compounds interfering with thyroid hormone signalling in complex environmental mixtures
Petra Mikušová

Environmental pollutant mixtures can elicit various endocrine disrupting effects, but the effect drivers are often unknown, since their identification is very challenging. Some environmental pollutants can disrupt thyroid hormon transport by plasma protein transthyretin (TTR), which can lead to neuro/developmental or metabolic disorders. Pull-down assay is a novel method we developed and optimized for the identification of TTR ligands from environmental complex mixtures and applied it to water samples. It is based on protein engineering (using plasmid-E.coli transformation), binding of TTR ligands to the TTR protein on molecular leve, identification and confirmation of the ligands through non/target HRMS analysis.

Liver on fire? Exposure to PFAS and PAHs in relation to cardiometabolic health (CELSPAC-FIREexpo STUDY)
Nina Pálešová

Firefighters are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs, released during combustion) and per- and polyfluoroalkyl substances (PFAS, used in firefighting foams and protective gear), which can lead to adverse health effects such as cardiometabolic syndrome. However, these relationships in firefighters are investigated very weakly.

CELSPAC-FIREexpo study includes 52 professional firefighters, 58 newly recruited firefighters and 54 non-firefighters (control group). The relationships between the exposure (6 PFAS, 6 OH-PAHs) and biomarkers of cardiometabolic health (alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (BIL)) and levels of serum lipids (total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG)) were investigated using multiple linear regression (MLR, for individual compounds) and Bayesian weighted quantile sum regression (BWQS, for mixture of compounds).

Positive associations between exposure to PFAS and PAHs mixture and BIL, CHOL and LDL were observed in BWQS model (β=28.6%, 29.5% and 26.7%, respectively). No statistically significant associations were detected in MLR. The results suggest that higher exposure to a mixture of these compounds is associated with an increase in BIL and the alteration of serum lipids, which can result in an unfavourable cardiometabolic profile, especially in occupationally exposed firefighters.

A novel method of stress measurement based on thermodynamics
Results from the chill ice ii space analog mission
Lucie Ráčková

This project aimed to measure markers of stress response in analog astronauts during the 7days long space analog mission, and to validate use of prototype for Stress Entropic Load (SEL) measurement in context of cave-based space analogue mission.

The SEL is a novel model for stress assessment based on thermodynamics. It quantifies the accumulation of entropy produced by specific individual as a response to given stressor or combination of stressors independently of their character. Hence, allows comparing stress across individuals and contexts objectively.

CHILL-ICE 2022 was an analog mission based in 100m depth of Iceland lava tubes, because of high geological resemblance to the Moon. A crew of 3 analog astronauts were deploying, assessed its suitability for long-term settlement and conducted research.

Analog astronauts were measured 5 times: pre-mission, three times during the mission, and post-mission. On the pre-mission and post-mission, two analog astronauts were measured as well. Measurements consisted of 5-minutes resting phase and 5-minutes Psychomotor Vigilance Task. Analog astronauts measured themselves at least 30m after waking up, on an empty stomach. Based on the measurements, we calculated SEL, HRV (pNN50), parameters of vigilance, and their trajectories for each individual. Results are descriptively compared as a series of cases.

Impact of PFAS exposure on human immunity
Barbora Rudzanová

Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants with multiple hazardous properties including immunomodulation potency. We aimed to investigate 1) the association between PFAS exposure and immune-mediated diseases (IMDs) and 2) the expression of genes associated with PFAS exposure in a population of Czech adults (CELSPAC: Young Adults cohort). Our results contribute to the body of literature that observes the immunomodulatory effect of PFAS exposure on the level of disease prevalence and further brought new information about underlaying deregulative mechanisms.

A seven years based characterisation of aerosol light scattering properties at Central European rural site: Variability and Source apportionment
Lenka Suchánková

Atmospheric aerosols have direct (scattering and absorption of light) and indirect (lifetime and properties of clouds) effects on the radiative forcing of Earth's climate. These effects play a crucial role in the estimation of climate models. The aim of this study is to determine the temporal variability of the optical properties measured by nephelometer TSI 3653 at a rural background site NAOK and aerosol source apportionment. The annual decreasing scattering trend and increased aerosol cooling effect were observed, suggesting a decrease in aerosol concentration and chemical composition change in 2012-2019. No specific aerosol sources were identified, supporting the background character of the station.

The Effect of Intrapartum Antibiotics Prophylaxis on Neonatal Gut and Oral Bacteriome
Eliška Pivrncová

The administration of intrapartum antibiotics prophylaxis (IAP) is commonly used in cesarean section and for the prevention of early-onset Group-B-streptococci infection. Since IAP may influence the microbiome development in neonates, our pilot study aimed to characterize the gut and oral bacteriome changes between neonates grouped according to their exposure to antibiotics during the delivery and sampling time in the first week of their life. 16S rDNA sequencing revealed differences in bacterial abundance in transitional stool samples, but not in meconium samples. Moreover, IAP influenced the oral bacteriome of neonates within 48 hours after birth. However, the effect of IAP on oral bacteriome seems to be suppressed later in the first week of their life.

Protein Learning for Solubility Design
Jan Velecký

Protein solubility is an attractive target in protein engineering mainly due to its relation to yields in protein production in chemical or pharmaceutical industries. However, we have a limited understanding of solubility determinants and the effects on solubility upon mutation. Furthermore, the available mutational data have mostly been scattered in the literature. We collected these data into SoluProtMutDB, making them available in a unified format and curated for the community. The collected data enables training of advanced machine learning models, such as models fusing graph representations with convolutional neural networks. We tuned such a model for protein 3D data and planned to adapt it to predict mutational effects.

The importance of a comprehensive toxicity assessment of nanopesticides in the environment: comparing toxic effects of tebuconazole in different formulations on the nematode C. elegans
Mahleh Eghbalinejad

Nanotechnology in agriculture is offering chances to develop more effective pesticides by improving the functionality of active substances, in addition to changing their environmental fate and risk. We prepared, characterized different formulations of nanopesticide and their risks toward Caenorhabditis elegans were assessed. Toxicity assessment of different formulations of TBZ showed varying effects. NFs showed higher toxicity on C. elegans. Experiments with the pure carriers revealed that the higher toxicity of Lipid- based nanoformulation was mainly due to stronger effects of lipid carrier compared to polymeric carriers, suggesting mixture toxicity of nanoparticles and active substance. Overall, these in vivo tests highlight that comprehensive toxicity testing of NPs is required to allow a reliable risk assessment.

Assessing Steatosis-Related Effects of Endocrine Disruptors: A Comparative Study of 2D and 3D In Vitro Approaches
Felipe Grosso Marina

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder characterized by the accumulation of triglycerides in liver cells. Recent evidence suggests that exposure to endocrine-disrupting environmental pollutants (EDs) may contribute to the development of NAFLD. However, current in vitro testing methods have limited ability to assess the "steatogenic potential" of EDs and related health hazards. To address this issue, a study tested the effects of ten selected EDs on human liver cell viability, lipid droplet accumulation, and altered expression of lipid metabolism genes using 2D and 3D models of HepG2 cells. The EDs tested included Bisphenols, Phthalates, Polyfluoroalkyl substances, Cadmium chloride, Pesticides, and Butyl-paraben.The results showed that six EDs, including DDE, BP, PFOA, BPF, DEHP, and CdCl2, increased lipid accumulation in liver cells, mostly at non-cytotoxic concentrations. These six EDs also upregulated genes involved in fatty acid and triglyceride synthesis, while BP and BPF increased fatty acid uptake and oxidation, and reduced fatty acid efflux. The study suggests that exposure to EDs increases the odds of developing NAFLD and highlights the potential of 2D and 3D hepatic models for in vitro assessment of adverse outcome pathways for hepatic metabolic diseases and the steatogenic potential of EDs and other environmental pollutants. Further investigation using 3D hepatospheroid cultures is ongoing.

The Mosaic Within: Unraveling Intratumor Heterogeneity in Colorectal Cancer
Martina Hrivňáková 

Colorectal cancer (CRC) is a heterogeneous disease, making it challenging to categorize and classify. To gain a deeper understanding of the relationships between gene expression and tumour morphology, six morphological patterns (morphotypes) were examined. The morphotypes included complex tubular (CT), desmoplastic (DE), mucinous (MU), papillary (PP), serrated (SE) and solid/trabecular (TB).
111 samples of colon cancers were analyzed, and regions of interest representing the six morphologies were digitally marked and macrodissected for RNA extraction. The results showed a whole landscape of changes at gene and pathway levels. CT and TB morphologies had activated pathways involved in proliferation processes, while TB also shared features with MU and DE morphologies. SE and PP morphologies shared characteristics such as moderately differentiated, low stromal content, and preserved crypt structure, indicative of the "serrated pathway." SE and PP exhibited similar activation of hallmark pathways, while also displaying unique hallmark pathways. The study highlights the importance of a morphological perspective in molecular classification and the need for multiple sampling locations to account for tumour heterogeneity.

Raman spectroscopy in
environmental research
Martin Kizovský

Raman microspectroscopy combined with microfluidic systems is useful for quasi-continuous flow-through analysis of liquid or suspended samples, such as microorganisms, micro and nanoplastics, and chemical pollutants. It is a non-destructive, fast, simple, and versatile method suitable for many applications. I employed several Raman microspectroscopy techniques to detect a variety of environmentally-relevent analytes, namely: 1) Detection of selenium content in microalgae Chlorella vulgaris by conventional Raman microspectroscopy. 2) Detection of submilimolar concentrations of glycerol using high-power Raman microspectroscope. The method was optimized for future monitoring of 1,2,3-trichloropropane enzymatic dehalogenation. 3) Detection of micro and nanoplastics using optical micromanipulation methods, such as Raman tweezers of optical printing. Raman tweezers allowed to distinguish microplastic particles from different parts of a degraded surgical facemask and the optical printing enabled detection of polystyrene nanobeads as small as a few tens of nm.

Liu Runze

Developing a battery of in vitro assays targeting key molecular initiation events in thyroid hormone regulation to assess Thyroid Hormone-Disrupting Chemicals
Liu R., Novák J., Hilscherová K.
RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic

This study developed and optimized in vitro assays to evaluate potential thyroid hormone-disrupting chemicals (TDCs) using an adverse outcome pathway (AOP) network approach. The battery addresses priority molecular initiation events (MIEs) in thyroid hormone regulation, including thyroperoxidase (TPO) inhibition and thyroxine-transthyretin (T4-TTR) displacement. The effects of TDCs on TH receptor signalling and AhR-mediated activity involved in TH metabolism were also assessed. The battery was employed to characterize effects of 20 prioritised chemicals with human exposure relevance, including environmental pollutants, natural compounds, and pharmaceuticals. These assays can reduce animal testing and indicate TDCs of risk to human and wildlife health.

Long-range atmospheric transport of currently-used pesticides over Europe
Ludovic Mayer

Current assumptions about the currently-used pesticides have led to the belief that their long-range atmospheric transport (LRAT) is unlikely. However, recent evidence of their presence in remote arctic air calls this assumption into question. To address this discrepancy, we sampled pesticides at 29 sites across Europe and the Arctic in spring 2020. Our findings identified 22 pesticides as prone to LRAT, including 15 approved for agricultural use and 7 banned in the EU. These results show the need for a revision of the current pesticide risk assessment methods in regards to their persistence and LRAT potential.

Study on the effects of cyanotoxins using advanced 3D in vitro liver model
Roy Chowdhury Riju

Hepatotoxic cyanobacterial toxins (cyanotoxins) chiefly, cylindrospermopsin (CYN) and microcystin-LR
(MC-LR) have been implicated in the etiology of chronic liver diseases, including metabolic disorders
and even promotion of liver cancer. 3D scaffold-free HepG2 spheroid cultures and collagen-based 3D
HepaRG cultures (Hepoid-HepaRG) were used to study the alterations of cellular and molecular events
linked to acute and chronic liver diseases. While, HepG2 spheroids served as a suitable model to study
the steatogenic potential of CYN at non-cytotoxic concentrations (1µM), Hepoid-HepaRG served as a
suitable model to study the toxicity effects of MC-LR at non-cytotoxic concentrations (0.1 µM).

Transcriptomic profiling of asthma, atopic eczema and allergies and their combinations
in Czech adult population
Hana Vespalcová

Asthma, atopic eczema and allergies are widespread immune-mediated diseases that often occur together. However, the molecular signature differs within the diseases and their combinations, the deregulation mechanism remain understudied. Therefore, to investigate gene expression and pathway disorders in immune-mediated diseases, we analyzed blood transcriptome of the adult participants from CELSPAC cohort study. We observed nearly 150 genes differentially expressed in atopic triad, 20 of them were directly involved in immunological pathways. Other 400 immune-related genes were found altered across all tested groups. 15 of them showed differential expression between contact dermatitis and IgE-mediated allergies. Moreover, we observed about 200 significant changes in immune gene networks and metabolic pathways associated with innate immune response, T cells or B cells in all groups. Such investigation help to understand the disease machinery and thus improve the future mitigation strategies.

Ishita Virmani

Exposure to real-life organochlorine chemical cocktails is suspected of contributing to male infertility. While previous studies have investigated their effects, the mechanisms behind their toxicity are yet to be elucidated. In this study, I aimed to explore the impact of a real-life cocktail of organochlorine chemicals on lipid accumulation and profile using murine Leydig Tm3 cells. I used an image-based assay and improved single-well liquid chromatography-mass spectroscopy (LC-MS) in a 96-well plate format. My results showed this cocktail caused lipid accumulation and affected various lipid species in lipid metabolism, leading to lipotoxicity and hormone disbalance. My research adds to the evidence supporting the contribution of environmental contamination by organochlorines to decreasing trends in male reproductive health.

Adverse outcome pathway linking nuclear receptor overactivation to feeding disruption
Audrey Xuan Phan

Retinoid signaling is crucial for development and homeostasis across vertebrates. Moreover, retinoid-like activities detected in Czech Republic reservoirs and for several triazole-fungicides have been associated with teratogenic effects in zebrafish larvae.

The study focuses on the development of adverse outcome pathway (AOP) leading to impairment in zebrafish early development, namely craniofacial malformation, posterior swim bladder inflation, and regulatory endpoints feeding disruption and survival. This brings together data for implementing AOP knowledge into risk assessment. Results indicate that the teratogenicity induced by retinoid disruption leads to 50% inhibition of feeding (7dpf) and ~90% mortality (14 dpf) at 1 ug/L all-trans-retinoic acid.