Loss of Inhibin Negative Feedback to Pituitary Gonadotropes Leads to Enhanced Ovulation but Pregnancy Failure in Mice
Bibliographic record
Abstract
Follicle-stimulating hormone (FSH) is an essential regulator of ovarian function. Inhibins are transforming growth factor β (TGFβ) family ligands produced in the gonads that suppress FSH synthesis by pituitary gonadotrope cells. Inhibins require a coreceptor, betaglycan or TGFBR3L, to mediate their actions. Female mice with a gonadotrope-specific knockout (KO) of betaglycan or global deletion of Tgfbr3l have increased FSH activity or levels and produce larger litters compared to controls. Females with both coreceptors knocked out (hereafter dKO) have dramatically increased circulating FSH, ovulate about 4 times as many eggs in natural cycles as controls but are infertile. Here, we show that dKO females show an increased number of implanted embryos at 7.5 days post coitum (dpc) but that their pregnancies fail around mid-gestation. Wild-type surrogates give birth to live young following transplantation of embryos from control or dKO females. Conversely, control but not dKO females can carry wild-type embryos to term, suggesting that the maternal environment in dKO mice cannot support full-term pregnancies. Elevated estradiol (E2) levels are deleterious to pregnancy in mice, and we detected increased E2 production in ovaries of pregnant dKOs. Treatment of these animals with aromatase inhibitors or a selective estrogen receptor degrader increased fetal survival. The results indicate that loss of inhibin action in murine gonadotropes results in excess E2 during pregnancy that precludes successful pregnancy.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".