The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Uterine Artery Function in a Rat Model of Advanced Maternal Age
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».