The use of traditional and alternative methods to study endocrine disruption in model avian species
Notice bibliographique
Résumé
Toxicity testing of chemicals is integral to environmental hazard determination and risk assessment. Traditional whole animal (in vivo) testing methods are resource-intensive and raise ethical concerns pertaining to animal use. This has led to a surge in the development of alternative methods (cells and tissues) to screen and prioritize chemicals. Despite the promise shown by such methods, little is known about how they perform against whole animal tests. Overall, this thesis aimed to advance knowledge on A) traditional and alternative toxicity testing methods, and B) the effects of 17β-trenbolone (17βT- an endocrine disrupting chemical used in livestock as a growth promoter) in model avian species. The specific aims were to 1) use in vivo exposures and next-generation RNA-Sequencing to examine sex- and developmental stage-related differences in the hepatic transcriptome of Japanese quail (JQ, Coturnix japonica) exposed to 17βT; Aim 2) assess molecular and biochemical effects on the quail endocrine system during early stages of in vivo exposure to 17βT; Aim 3) compare effects of chemicals on gene expression in three alternative methods: hepatocytes, liver slice culture, and in ovo liver of white leghorn chicken (Gallus gallus domesticus); and Aim 4) outline key challenges, opportunities, and monetary costs, time and number of animals associated with traditional and alternative testing. In Aim 1, analysis of the quail hepatic transcriptome indicated that early life stages may be more vulnerable to endocrine disruption than adults. Differentially expressed genes were related to processes including cell proliferation, and transport and metabolism of lipids and proteins. In Aim 2, analyses of the JQ endocrine pathway revealed significant differences in plasma hormone levels in exposed males and females that fluctuated over the duration of exposure, but no changes in the expression of associated genes, implying that metabolic pathways and other receptors may be involved in the mechanisms by which 17βT impairs the endocrine system. In Aim 3, hierarchical clustering analysis of gene expression results across three alternative methods showed similarities between liver slice culture and in ovo liver, while hepatocytes were more different. In Aim 4, bibliometric searches of resource-related costs from various sources showed that, realistically, the status quo in toxicity testing will not be able to provide toxicity data for all existing and emerging chemicals. In summary, this work demonstrated the potential of liver slices as alternatives in toxicity testing; further, this work showed that even using traditional methods results may vary depending on factors such as sex, developmental stage, and exposure duration. This thesis advances knowledge on two fronts: A) the potential of alternative testing methods to aid in their future implementation and the reduction of traditional methods in chemical toxicity testing, and B) the importance of including aforementioned factors while examining molecular and biochemical endpoints in toxicity studies.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».