PMID- 35883766
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 7
DP  - 2022 Jun 28
TI  - The Effect of Tauroursodeoxycholic Acid (TUDCA) Treatment on Pregnancy Outcomes 
      and Vascular Function in a Rat Model of Advanced Maternal Age.
LID - 10.3390/antiox11071275 [doi]
LID - 1275
AB  - 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-eIF2alpha 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-eIF2alpha and CHOP expression, reduced fetal weight, reduced litter size, and 
      impaired uterine artery relaxation. In the aged dams, TUDCA treatment reduced 
      phospho-eIF2alpha 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.
FAU - Pasha, Mazhar
AU  - Pasha M
AD  - Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
FAU - Kirschenman, Raven
AU  - Kirschenman R
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
FAU - Wooldridge, Amy
AU  - Wooldridge A
AUID- ORCID: 0000-0002-2914-7693
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
FAU - Spaans, Floor
AU  - Spaans F
AUID- ORCID: 0000-0002-8024-4413
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
FAU - Cooke, Christy-Lynn M
AU  - Cooke CM
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
FAU - Davidge, Sandra T
AU  - Davidge ST
AD  - Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
AD  - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 
      2S2, Canada.
AD  - Women and Children's Health Research Institute, University of Alberta, Edmonton, 
      AB T6G 1C9, Canada.
LA  - eng
GR  - FS154313/CAPMC/CIHR/Canada
GR  - N/A/Women and Children's Health Research Institute/
GR  - FoMD 75th Anniversary Award/University of Alberta/
GR  - Graduate Studentship Award/Women and Children's Health Research Institute/
PT  - Journal Article
DEP - 20220628
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9312116
OTO - NOTNLM
OT  - advanced maternal age
OT  - endoplasmic reticulum stress
OT  - endothelium-dependent relaxation
OT  - pregnancy outcomes
OT  - tauroursodeoxycholic acid
OT  - wire myography
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/06/28
CRDT- 2022/07/27 01:07
PHST- 2022/05/27 00:00 [received]
PHST- 2022/06/22 00:00 [revised]
PHST- 2022/06/24 00:00 [accepted]
PHST- 2022/07/27 01:07 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/06/28 00:00 [pmc-release]
AID - antiox11071275 [pii]
AID - antioxidants-11-01275 [pii]
AID - 10.3390/antiox11071275 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Jun 28;11(7):1275. doi: 10.3390/antiox11071275.