The effect of tauroursodeoxycholic Acid (TUDCA) treatment on placental endoplasmic reticulum (ER) stress in a rat model of advanced maternal age.

Autor: Pasha M; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Kirschenman R; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Wooldridge A; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Spaans F; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Cooke CM; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Davidge ST; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Apr 06; Vol. 18 (4), pp. e0282442. Date of Electronic Publication: 2023 Apr 06 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0282442
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Pasha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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