HORMONAL REGULATION OF THE NOTCH PATHWAY GENES IN THE GRANULOSA CELLS DURING GONADOTROPIN INDUCED OVARIAN FOLLICULAR GROWTH
Bibliographic record
Abstract
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)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".