Metabolomic Profiling of Biomarkers Indicative of Ancestral and Lifetime Adversity in a Two-Hit Stress Model
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Résumé
Introduction: Chronic prenatal maternal stress (PNMS) can have adverse effects on the developing fetus and lifetime health. The effects depend on the number of stressors individuals are exposed to. Over-activation of the mother’s stress response also potentially triggers epigenetic marks that can be transmitted to several generations of offspring. To date, very little research has focused on how exposure to ancestral PNMS affects an individual’s response to both chronic and acute stress throughout their lifetime. The purpose of this study was to investigate if exposure to ancestral PNMS puts an individual at an evolutionary advantage or disadvantage with respect to their altered stress response. This study utilized a rat model of ancestral PNMS to explore the response of the metabolome to both acute and chronic stress. Methods: Forty-eight male rats from the third filial generation were derived from three different lineages: (1) a transgenerational PNMS lineage where only the F0 mother was exposed to stress; (2) a multigenerational PNMS lineage where the mother from each generation was exposed to stress; and (3) a control lineage where there was no experimental stress exposure. Each of these groups were split in two; an acute stress group and a chronic stress group. Plasma was collected from each animal, processed to extract the water-soluble metabolites, added to NMR buffer, and pipetted into NMR tubes. NMR spectra were acquired and the data underwent a data reduction step (binning), normalization, scaling, and both univariate and multivariate statistical testing. These tests identified spectral peaks from metabolites that had been significantly altered across comparison groups. Chemometric software was utilized to determine the identity of altered metabolites and pathway topology analysis was performed. Results: Multivariate and univariate statistical tests indicated that exposure to chronic stress in ancestrally stressed rats creates significant alteration in the metabolomic profile when compared to control animals. No differences were observed in the case of acute stress. Conclusions: Our results support the hypothesis that ancestral and lifetime stress cumulatively affect the metabolome. A subset of metabolites can potentially act as biomarkers of stress during pregnancy. This procedure may aid in the development of new predictive and diagnostic strategies in precision medicine approaches. *Indicates presenter
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 découle