ArticlePloS one2023
The effect of tauroursodeoxycholic Acid (TUDCA) treatment on placental endoplasmic reticulum (ER) stress in a rat model of advanced maternal age.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Targeting endoplasmic reticulum stress for neuroprotection in ischemia-reperfusion injury: mechanisms and therapeutic approaches.Molecular biology reports · 2026Review
- Review
- Navigating Cellular Stress: Endoplasmic Reticulum Stress and the Unfolded Protein Response in the Molecular Pathogenesis of Preeclampsia.Cell biochemistry and biophysics · 2025Review
- Liver as a metabolic sensor in gestational diabetes: Implications for offspring's liver and diabetes risk.World journal of hepatology · 2025Review
- Impact of excessive hypercholesterolemia in pregnancy on the placentas of the male and female offspring.Scientific reports · 2025Article
- Understanding the intersection between placental development and cancer: Lessons from the tumor suppressor BAP1.Communications biology · 2024Review
- LIM homeobox 1 (LHX1) induces endoplasmic reticulum stress and promotes preterm birth.Heliyon · 2024Article
- Tauroursodeoxycholic acid as a beneficial modulator for developmentally programed chromatin structure around specific genes.Frontiers in endocrinology · 2024Article
- A stress paradox: the dual role of the unfolded protein response in the placenta.Frontiers in endocrinology · 2024Review
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6 authors at 1 institution in 1 country.
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Abstract
Advanced maternal age (≥35 years) is associated with an increased risk of pregnancy complications such as fetal growth restriction and preeclampsia. We previously demonstrated poor pregnancy outcomes (reduced fetal body weight), altered vascular function, and increased expression of endoplasmic reticulum (ER) stress markers (phospho-eIF2α and CHOP) in mesenteric arteries from a rat model of advanced maternal age. Further, treatment of aged dams during pregnancy with an ER stress inhibitor, tauroursodeoxycholic acid (TUDCA) increased fetal body weight (both male and female), tended to improve uterine artery function, and reduced expression of phospho-eIF2α and CHOP in systemic arteries. Placental ER stress has been linked to poor pregnancy outcomes in complicated pregnancies but whether placental ER stress is evident in advanced maternal age is not known. In addition, sex-specific changes in the placental labyrinth and junctional zones from male and female offspring in advanced maternal age have not been investigated. Therefore, the current study aimed to investigate the effect of TUDCA intervention on placental ER stress. We hypothesize that placental ER stress is increased in a rat model of advanced maternal age that is alleviated by TUDCA intervention for both sexes. Placental ER stress markers (GRP78, phospho-eIF2α, ATF-4, CHOP, ATF-6α, and sXBP-1) were quantified by Western blot in placentas from male and female offspring; the labyrinth and junction zones were analyzed separately. In the placental labyrinth zone from male offspring, only GRP78 (p = 0.007) was increased in aged dams compared to young dams; TUDCA treatment reduced the placental expression of GRP78 in aged dams (p = 0.003). In addition, TUDCA reduced the levels of phospho-eIF2α (p = 0.021), ATF-4 (p = 0.016), and CHOP (p = 0.012) in aged dams but no effect was observed in young TUDCA-treated dams. In the placental labyrinth zone from female offspring, an increased level of phospho-eIF2α (p = 0.005) was observed in aged dams compared to young dams, and TUDCA treatment had no effect in both young and aged groups. In the placental junctional zone from male and female offspring, no changes in the expression of GRP78, phospho-eIF2α, ATF-4, CHOP, and ATF-6α was observed with or without TUDCA treatment in both young and aged groups, however, a reduced expression of sXBP-1 protein was observed in from both male (p = 0.001) and female (p = 0.031) placentas from aged-TUDCA treated dams compared to aged control. In conclusion, our data highlight the complexity and sex-specificity of ER stress responses in advanced maternal age with TUDCA treatment maintaining ER stress proteins to basal levels and improving fetal growth in both male and female offspring.
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