1 CUMULUS CELLS PROTECT OOCYTES AGAINST POTENTIAL LIPOTOXICITY FROM ELEVATED FREE FATTY ACID CONCENTRATIONS IN FOLLICULAR FLUID
Bibliographic record
Abstract
Metabolic conditions characterized by elevated free fatty acid levels in the blood are often associated with reduced fertility performance. Increased concentrations of saturated free fatty acids can induce lipotoxicity in cumulus–oocyte-complexes in vitro, while unsaturated fatty acids like oleic acid are mostly harmless and able to counteract the impact of saturated fatty acids (Aardema et al. 2011 Biol. Reprod. 85, 62–69). This study investigates the impact of elevated free fatty acids in the blood on the follicular fluid and the lipid of cumulus and oocytes derived from these follicles. Furthermore, in vitro maturing oocytes were exposed to free fatty acid concentrations measured in follicles of control and metabolically stressed animals from this study to determine the impact on oocyte developmental competence. Cyclic heifers (n = 12) were synchronized (7 days CIDR®) and superstimulated from Day 10 of the synchronized cycle [4 days of Folltropin-V® (Bioniche Animal Health Inc., Belleville, ON, Canada) in decreasing doses; in total 200 mg]. Heifers received ad libitum grass silage, apart from the experimental group (n = 6), which was metabolically stressed during the period of superstimulation. Ovaries were collected by ovariectomy at final maturation, 22 h after the induced LH peak. Follicular fluids and cumulus–oocyte complexes (COC) were collected from follicles of =8 mm. To determine the free fatty acid and lipid composition, blood, follicular fluid, cumulus cells, and oocytes were analyzed with mass spectrometry. The COC (4 runs, 400 per group) derived from slaughterhouse ovaries were in vitro matured in a standard medium without or with the dominating free fatty acids, saturated palmitic and stearic and unsaturated oleic acid, in concentrations measured in follicular fluid of control (80, 70, and 100 µM) and experimental heifers (150, 100, and 200 µM) and fertilized and cultured until the blastocyst stage. Culture data were analyzed by one-way ANOVA and lipid data by two-sample t-test (P = 0.05 considered significant). Procedures were approved by the Institutional Animal Care and Use Committee. Metabolic stress resulted in elevated free fatty acid levels in blood (from 430 ± 70 to 1048 ± 190 µM) and follicular fluid (from 357 ± 72 to 670 ± 133 µM), with relatively high oleic acid concentrations in follicular fluid (+10%). The increased levels of free fatty acids in follicular fluid resulted in a massive increase of fatty acids in the cumulus cells, but oocytes did only show marginal changes. In line with this, maturation in the presence of elevated palmitic, stearic, and oleic acid did not impair oocyte developmental competence and resulted in comparable blastocyst rates for the standard medium and the free fatty acid control and metabolic stress medium (31 ± 8.7, 34 ± 7.8, and 28 ± 1.7%). Thus, cumulus cells appear to protect oocytes against potential lipotoxicity from elevated free fatty acid concentrations by the accumulation of these fatty acids. This work was funded by Pfizer Animal Health.
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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) | 0.003 | 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".