Uro‐genital Development in Juvenile Sprague‐Dawley Rats: a Histomorphologic and Immunohistochemical Study
Notice bibliographique
Résumé
Preclinical juvenile toxicity studies are crucial in the development of new drugs intended to be administered to children. While the normal histomorphological features of the uro‐genital systems in mature rats have been described, the physiological developmental changes occurring in neonatal and juvenile rats remain incompletely characterized. As the rat is the most commonly used species in toxicology studies, it is pivotal to further understand the normal tissue remodeling events, including apoptosis and cell proliferation occurring during the juvenile phase, in order to prevent mistaking these changes for pathological lesions. The objective of this study was to describe the key histomorphologic postnatal events occurring in the uro‐genital system of Sprague‐Dawley rats from birth to postnatal day (PnD) 30, with a special focus on cell proliferation and apoptosis. Formalin‐fixed and paraffin‐embedded kidneys, urinary bladder, ovaries, testes, epididymis, uterus and vagina were obtained from 51 Sprague Dawley rats divided in 13 timepoints according to age (PnD 1, 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. The ratios of the testes and kidney weights relative to the body weight was calculated for each timepoint, reaching a maximum value between PnD10 and PnD15 and on PnD30, respectively. Immunohistochemistry staining was performed to highlight apoptosis (caspase‐3) and cell proliferation (Ki‐67) when relevant. Hematoxylin and eosin slides revealed an increased cellularity in the kidney at PnD1 with the presence of a distinct nephrogenic zone in the outer one‐fourth of the cortex and contained different stages of developing nephrons. Nephrogenesis was characterized by abundant cell death and mitoses progressing from the outer cortex to the medulla, and ceased mostly by PnD14, as only few mitoses were observed at the cortico‐medullary junction at PnD21. At PnD1, the cuboidal epithelium lining the luminal surface of the urinary bladder consisted of two distinct cell layers and became 3 to 4 layers thick by PnD21. On PnD1, the ovarian parenchyma was hypercellular and diffusely composed of pockets of oocytes enveloped in stromal cells and, by PnD 26, a sharply demarcated cortico‐medullary separation was noticeable. The first uterine glands became visible around PnD14, whereas scattered apoptotic epithelial cells were still present up to PnD26. The vaginal epithelium showed multifocal mucification mixed with few apoptotic cells starting on PnD24. At PnD1, the seminiferous tubular epithelium was 1 to 2 layers thick, composed of spermatogonia and sertoli cells, and a seminiferous lumen was rarely noticeable. Pachytene spermatocytes were observed around the second week of life, while round spermatids were first visible on PnD26. This study showed that the urogenital system of Sprague‐Dawley rats is immature at birth and that different organs develop at various rates during the first month of age. Programmed cell death and cell proliferation coexist and should not be misinterpreted as drug‐related effects in toxicologic 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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| 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 | 0,000 |
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 ».