期刊
ANTIOXIDANTS
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/antiox11071275
关键词
advanced maternal age; pregnancy outcomes; endoplasmic reticulum stress; tauroursodeoxycholic acid; wire myography; endothelium-dependent relaxation
资金
- Canadian Institutes of Health Research (CIHR) Foundation [FS154313]
- Stollery Children's Hospital Foundation
- Alberta Women's Health Foundation through the Women and Children's Health Research Institute (WCHRI)
- WCHRI Graduate Studentship Award
- Faculty of Medicine & Dentistry 75th Anniversary Award from the University of Alberta
The study indicates that advanced maternal age is associated with endoplasmic reticulum (ER) stress, and the ER stress inhibitor TUDCA may improve pregnancy outcomes.
Advanced maternal age (>= 35 years) increases the risk of vascular complications in pregnancy that can result in fetal growth restriction and preeclampsia. Endoplasmic reticulum (ER) stress has been linked to adverse pregnancy outcomes in these complicated pregnancies. However, the role of ER stress in advanced maternal age is not known. We hypothesize that increased ER stress contributes to altered vascular function and poor pregnancy outcomes, and that treatment with the ER-stress inhibitor TUDCA will improve pregnancy outcomes. First, young and aged non-pregnant/pregnant rats were used to assess ER stress markers in mesenteric arteries; mesenteric artery phospho-eIF2 alpha and CHOP expression were increased in aged dams compared to young dams. In a second study, young and aged control and TUDCA-treated dams were studied on gestational day (GD) 20 (term = 22 days). TUDCA treatment was provided via the drinking water throughout pregnancy (GD0-GD20; calculated dose of 150 mg/kg/day TUDCA). ER stress markers were quantified in mesenteric arteries, blood pressure was measured, pregnancy outcomes were recorded, mesenteric and main uterine arteries were isolated and vascular function was assessed by wire myography. Aged dams had increased phospho-eIF2 alpha and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2 alpha and CHOP expression, reduced blood pressure, improved fetal body weight, and tended to improve uterine artery function compared to control-treated aged dams. In conclusion, our data illustrate the role of ER stress, as well as TUDCA as a potential therapeutic that may benefit pregnancy outcomes in advanced maternal age.
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