OR09-03 Loss of Inhibin Negative Feedback In The Pituitary Leads To Enhanced Ovulation But Pregnancy Failure In Mice
Bibliographic record
Abstract
Abstract Disclosure: Y. Lin: None. E. Brule: None. M. Cowan: None. U. Boehm: None. D.J. Bernard: None. Loss of inhibin negative feedback in the pituitary leads to enhanced ovulation but pregnancy failure in mice Follicle-stimulating hormone (FSH) is an essential regulator of gonadal function, particularly in females. Inhibins are TGFβ family ligands made in the gonads that suppress FSH synthesis. Inhibins require a co-receptor, betaglycan or TGFBR3L, to mediate their actions in pituitary gonadotrope cells. Female mice with a gonadotrope-specific knockout of betaglycan or global deletion of Tgfbr3l exhibit increased ovarian follicle development, numbers of ovulated eggs, and litter sizes compared to controls. Females with both co-receptors knocked out (hereafter dKO) show dramatic increases in FSH levels, numbers of antral follicles and corpora lutea, serum progesterone levels, and ovarian aromatase expression. They ovulate 3-4 times as many eggs in natural cycles compared to control females. dKO females can become pregnant and show an increased number of implanted embryos at 7.5 days post coitum (7.5 dpc). Nevertheless, dKO females do not give birth to live offspring. By 10.5 dpc, the weight of the fetoplacental unit is decreased in dKO females, and many embryos display morphological abnormalities. By 14.5 dpc, most embryos in dKO females are either dead or resorbing. Wild-type surrogates give birth to live young following transplantation of embryos from control or dKO females. Conversely, control but not dKO females carry wild-type embryos to term. These data suggest that the maternal environment in dKO mice cannot support full-term pregnancies. Based on the hormonal profile of the cycling females, we suspected a deleterious effect of elevated estrogens. Consistent with this idea, treatment with the aromatase inhibitor anastrozole increased fetal survival in some dKO mice, suggesting a role for estrogens in embryo death. We are currently more thoroughly characterizing the maternal hormonal environment throughout gestation and investigating placental structure/function to gain more insight into the precise nature of the pregnancy failure. Our results will show how loss of inhibin action in the pituitary impede embryo survival and whether pregnancy loss is linked to increases in FSH. Presentation: Friday, June 16, 2023
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".