HORMONAL REGULATION OF THE NOTCH PATHWAY GENES IN THE GRANULOSA CELLS DURING GONADOTROPIN INDUCED OVARIAN FOLLICULAR GROWTH
Notice bibliographique
Résumé
The ovarian follicular growth leading up to ovulation involves proliferation and differentiation of the granulosa cells. The final periovulatory differentiation of the granulosa cells, which is begun by LH surge, is characterized by transition from proliferative estradiol producing cells to non-proliferative progesterone producing cells. Among the myriad pathways that are involved in the cell fate decision, the intercellular Notch signaling assumes an important role, which is evidenced by the lethality due to genetic deletion of any one molecule of the pathway. While there is a sporadic evidence for the obvious existence of the Notch pathway in the ovary, the expression pattern of the molecular players of the Notch pathway and their temporal relationship with the granulosa differentiation is lacking. Thus, the objective of the present study was to determine the mRNA expression pattern of the molecules of the Notch signaling pathway including Notch-ligands and Notch-targets in conjunction with the molecular markers of granulosa cell differentiation. Immature C57BL/6J mice were superstimulated using a standard protocol to collect ovaries at various time points after the administration eCG and hCG. Total RNA was purified (RNeasy Micro Kit, Qiagen) from pure population of the granulosa cells of the antral follicles were collected by laser microdissection (Leica AS LMD). Upon real-time polymerase chain reaction analyses, it was revealed that the mRNA expression of Cyp19a1, Ccnd2, Gja1 were induced and peaked by 36 h post-eCG (P < 0.05) and were then down regulated (P < 0.05) by 4 h post-hCG administration, while the mRNA expression of Star was upregulated, by 2-folds (P < 0.05), at 4 h post-hCG. These results are indicative of the well known pattern of eCG/FSH dependent differentiation of the granulosa cell followed by their differentiate into luteal cells induced by hCG administration. The mRNA expression of Notch1 and Notch3 and a Notch-ligand, Jag1 was upregulated by 5–10 folds and peaked at 36–48 h in response to eCG administration (P < 0.05). While their expression was dramatically downregulated upon hCG stimulation by as early as 4 h posttreatment (P < 0.05). The expression pattern of Hes1 and Hes6 (P < 0.05) closely followed that of Notch1 and Notch3 suggesting that the mRNA expression pattern of the Notch and its ligand underscored their functionality during the growth of the ovarian follicles. These findings demonstrate that the molecular players of the Notch pathway are hormonally regulated in granulosa cells during gonadotropin induced follicular growth. Finally, this study opens up new avenues to study the regulation of the Notch-signaling molecules using an established granulosa differentiation model, which may help to understand ovarian pathogenesis due to deregulation of the Notch pathway. RD supported by a fellowship from the Serono Foundation. (poster)
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 | 0,000 | 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) | 0,001 | 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 ».