Differential Expression Changes in Human Decidua With Term and Preterm Labor: Role for Upstream Targets in the Prostaglandin Pathway
Bibliographic record
Abstract
Abstract Introduction: Prostaglandins (PGs) are paracrine mediators thought to be important during pregnancy and labor. Synthesis of PGs is complex with three rate limiting steps, the second of which (PTGS2/cyclooxygenase) is a target for managing preterm labor, but this treatment is not always effective. It is suggested that alternate steps in the PG pathway may play distinct roles during labor and hence the potential as alternate targets for labor management. The first step of PG synthesis involves the action of phospholipase A2 (PLA2) enzymes, of which over a dozen isotypes are known. However, PLA2 expression and role in the decidua (maternal-fetal interface) is unknown. We hypothesize that distinct PLA2 isotypes are present within the decidua and play a role in term and preterm labor. To this end, we conducted an expression profile of PLA2 subtypes and related PG genes within human decidua and determined differential expression patterns with labor at term and preterm. Methods: Decidual samples from term (40wks) and preterm (26-37wks) Cesarean deliveries, were used to assess PG gene expression by RNAseq and qRT-PCR (n=7 preterm non-labor, n=11 preterm labor, n=31 term non-labor, n=31 term labor). Analyses were conducted using student’s t-test and one-way ANOVA to compare labor (non-labor vs labor) or with gestation (preterm vs term) and adjusted for multiple testing using the Benjamini-Hochberg method. Results: RNAseq analysis identified 30 highly expressed PG genes in decidua, of which 12 had not been previously reported in the uterus, including 7 PLA2 isotypes. Confirming previous work, expression of PTGS2 was higher with labor (p=0.011). In contrast, we demonstrate that PLA2 isotype expression is lower with labor, with further differences between term and preterm samples. With term labor, expression of PLA2 isotype 2D was lower compared to non-labour (p=0.047). Meanwhile, preterm labor was associated with lower expression of PLA2 isotype 16 (p=0.025) and 4C (p=0.026), compared to preterm non-labour. Epression of PLA2 subtypes 2A, 15 and 4A late was highest in late labor (p=0.016, 0.004, 0.03, respectively). Conclusion: The presence of multiple PLA2 subtypes within the decidua suggests the potential for fine tuning PG synthesis during pregnancy. Expression of PLA2 isotypes 16 and 4C was uniquely associated with preterm labor, suggesting these isotypes may play a role in the pathogenesis of preterm labor. Further investigation of the functional role of PLA2 isotypes may provide insight to a novel mechanism for preterm labor and identify potential targets for labor management.
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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".