MEK2 Is Essential for the Ovarian Response to the LHR Signal.
Bibliographic record
Abstract
Activation of the MEK-ERK signaling cascade regulates many gonadotropin-dependent ovarian functions but a detailed examination of these pathways in ovarian physiology is still missing. This is particularly important when one considers that there are two MEKs (MEK1 and MEK2) and two ERKs (ERK1 and ERK2) and mice that are null for MEK1 or MEK2 as well as mice that are null for ERK1 or ERK2 do not display the same phenotype. For example MEK1 null as well as ERK2 null mice die before birth, whereas MEK2 as well as ERK1 null mice are healthy and fertile. Here we examine the ovarian responses of MEK2 null mice (MEK2KO) to gonadotropins. Female MEK2KO mice display normal fertility. They also show normal follicular development during the estrous cycle or following an injection of PMSG. However, injection of hCG (after PMSG priming) into the MEK2KO mice increased the phosphorylation of ERK1/2 in the ovary to a lesser extent that in wt mice. This hCG injection also failed to promote a normal granulosa to luteal cells transition. Quantitative histological evaluation of fixed ovarian sections stained with H&E showed that MEK2KO mice displayed fewer corpora lutea, and an increased number of large antral follicles some of which contained unovulated oocytes. In line with these histological observations, the expression of CYP11a1 was reduced in MEK2KO ovaries as judged by Western blotting and immunohistochemistry. Many of the antral follicles as well as corpora lutea in the superovulated MEK2KO ovaries showed weak staining for CYP11a1 suggesting that terminal differentiation had not taken place. In contrast, the ovaries of superovulated wt mice showed mostly corpora lutea that were rich in CYP11a1. Lastly, real-time PCR analysis revealed that expression of ovarian aromatase and the LHR remain elevated after hCG injection in the PMSG treated MEK2KO mice. These findings show that the absence of MEK2 does not affect fertility but also does not support a full expression of the LH signal. The main defect in these mice seems to be a delay in the process of luteinization without a change in the ovulatory response. This work was supported by a grant from the National Institutes of Health (RO1-HD28962). (platform)
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".