The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Uterine Artery Function in a Rat Model of Advanced Maternal Age
Bibliographic record
Abstract
Introduction Advanced maternal age (AMA; ≥35 years) increases the risk of pregnancy complications and adverse pregnancy outcomes such as fetal growth restriction. Endoplasmic reticulum (ER) and oxidative stress have been linked to vascular dysfunction (i.e. reduced nitric oxide [NO] & increased endothelin‐1 [ET‐1] levels) in aging. Tauroursodeoxycholic acid (TUDCA) is an ER and oxidative stress inhibitor and has been shown to improve embryo development in vitro . However, whether treatment with TUDCA can help improve uterine vascular function and pregnancy outcomes in AMA has not been investigated. We hypothesize that TUDCA treatment will improve pregnancy outcomes and vascular function in a rat model of AMA. Methods Young (4 months) and aged (9.5 months of age; ~35 years in humans) pregnant control or TUDCA‐treated rats were studied on gestational day 20 (term=22 days). Following euthanasia, pregnancy outcomes (litter size, resorption sites, fetal weight, and placental weight) were recorded, and main uterine arteries were isolated. Endothelium‐dependent vasorelaxation to methacholine (MCh) was assessed by wire myography in the presence/absence of pan NO synthase inhibitor (L‐NAME). In addition, big‐endothelin‐1 (bET‐1) vasoconstriction responses were evaluated, in the presence/absence of endothelin converting enzyme (ECE) inhibitor (CGS). Data summarized as maximum vasodilation response (Emax) and analyzed by two‐way ANOVA with Sidak’s post‐test, p<0.05 was considered significant. Results Fetal body weights were reduced in AMA control rats compared to young dams (p<0.017), while TUDCA treatment tended to increase fetal body weight in AMA rats (p=0.067); TUDCA did not affect fetal body weight in the young dams. Placental weights, litter size and number of resorptions were similar in all the groups. The maximum relaxation (Emax) to MCh was impaired in the AMA dams compared to young dam (p=0.047), and this reduced relaxation was not evident in the TUDCA treated AMA dams. Ex vivo treatment with L‐ NAME showed an increased contribution of NO in young TUDCA treated rats (ΔEmax [differences in Emax]; p=0.043) compared to young control rats but not in AMA rats. Ex vivo treatment with CGS demonstrated reduced ECE conversion in young TUDCA treated rats (Emax; p<0.001), while CGS had no effect in the young control dams or both AMA groups. Conclusion Our study assessed TUDCA as an intervention to improve the pregnancy outcomes in a rat model of AMA. An increased fetal body weight suggests a beneficial effect of TUDCA in AMA pregnancies. However, contrary to our hypothesis, in young dams, TUDCA increased NO contribution and reduced ECE effect, but did not affect uterine artery function in AMA dams. Nevertheless, TUDCA has the potential to improve pregnancy outcomes in complicated pregnancies, but further studies are warranted.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".