The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age
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 i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1275 |
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| author | Mazhar Pasha Raven Kirschenman Amy Wooldridge Floor Spaans Christy-Lynn M. Cooke Sandra T. Davidge |
| author_facet | Mazhar Pasha Raven Kirschenman Amy Wooldridge Floor Spaans Christy-Lynn M. Cooke Sandra T. Davidge |
| author_sort | Mazhar Pasha |
| collection | DOAJ |
| description | 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-eIF2α 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-eIF2α and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2α 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. |
| first_indexed | 2024-03-09T03:46:10Z |
| format | Article |
| id | doaj.art-24e94f51bafd453cb013b4093a203477 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T03:46:10Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-24e94f51bafd453cb013b4093a2034772023-12-03T14:33:42ZengMDPI AGAntioxidants2076-39212022-06-01117127510.3390/antiox11071275The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal AgeMazhar Pasha0Raven Kirschenman1Amy Wooldridge2Floor Spaans3Christy-Lynn M. Cooke4Sandra T. Davidge5Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Physiology, University of Alberta, Edmonton, AB T6G 2R3, CanadaAdvanced 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-eIF2α 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-eIF2α and CHOP expression, reduced fetal weight, reduced litter size, and impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced phospho-eIF2α 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.https://www.mdpi.com/2076-3921/11/7/1275advanced maternal agepregnancy outcomesendoplasmic reticulum stresstauroursodeoxycholic acidwire myographyendothelium-dependent relaxation |
| spellingShingle | Mazhar Pasha Raven Kirschenman Amy Wooldridge Floor Spaans Christy-Lynn M. Cooke Sandra T. Davidge The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age Antioxidants advanced maternal age pregnancy outcomes endoplasmic reticulum stress tauroursodeoxycholic acid wire myography endothelium-dependent relaxation |
| title | The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age |
| title_full | The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age |
| title_fullStr | The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age |
| title_full_unstemmed | The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age |
| title_short | The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes and Vascular Function in a Rat Model of Advanced Maternal Age |
| title_sort | effect of tauroursodeoxycholic acid tudca treatment on pregnancy outcomes and vascular function in a rat model of advanced maternal age |
| topic | advanced maternal age pregnancy outcomes endoplasmic reticulum stress tauroursodeoxycholic acid wire myography endothelium-dependent relaxation |
| url | https://www.mdpi.com/2076-3921/11/7/1275 |
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