Cardio‐respiratory Development in Juvenile Sprague‐Dawley Rats: a Histomorphologic and Immunohistochemical Study
Notice bibliographique
Résumé
Juvenile toxicity studies have become an important and crucial focus of the preclinical drug industry. To accurately distinguish the potential detrimental effects of new drugs on the cardio‐respiratory system, it is essential to thoroughly define the normal tissue remodeling features characterizing the development and maturation of this system. The purpose of this study was to investigate the key histomorphological postnatal changes of the cardio‐respiratory system in Sprague‐Dawley rats from birth to postnatal day (PnD) 30, with a special focus on cell proliferation and apoptosis. Formalin‐fixed and paraffin‐embedded lung, trachea, heart and aorta were obtained from 51 Sprague Dawley rats divided in 13 timepoints according to age (PnD1, 2, 4, 6, 8, 10, 14, 17, 21, 24, 26, 28, and 30). Whenever possible, equal numbers of females and males were used in each group. Sections were cut at 4mm thickness and stained with hematoxylin and eosin. In addition, immunohistochemical demonstration of vimentin within lung samples and distinction between collagen and elastin fibers within the aortic wall with Masson's trichrome stain was performed. When relevant, immunohistochemistry staining was performed to highlight apoptosis (caspase‐3) and cell proliferation (Ki‐67). The ratio of heart weight relative to body weight was calculated for each timepoint and was higher at birth, then progressively decreased until PnD30. The rat heart was morphologically immature at birth and developed by cell hyperplasia over the perinatal period followed by cell hypertrophy around the third postnatal week. The newborn myocardium was hypercellular with less prominent cross‐striations, and mitotic figures and apoptotic bodies were frequently seen. The aortic wall progressively increased in thickness throughout the duration of the study as a result of an accumulation of extracellular matrix (collagen and elastic fibers). At birth, the trachea was lined by immature columnar ciliated epithelial cells, and submucosal glands became visible around one week after birth. The newborn rat had no alveoli but instead possessed large gas exchange units termed “primary saccules” characterized by highly cellular walls with a central sheet of connective tissue flanked on both sides by flattened cells (primary septa). An intense interstitial cellular proliferation was observed in the lungs between PND6 and PND14 resulting in new secondary septa, which were highly vimentin immunopositive. By the end of the third postnatal week, the septa underwent noticeable thinning and the lung parenchyma progressively matured, resulting in increased gas exchange surfaces. The findings described herein suggest that the cardio‐respiratory system of rats is immature at birth. The lungs and airways reached maturity 3 weeks after birth while cardiomyocyte hypertrophy was noticed until PnD30. The data generated will serve as background historical database that will be valuable when performing postnatal developmental toxicity studies. Support or Funding Information Mitacs
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».