PMID- 33607270
OWN - NLM
STAT- MEDLINE
DCOM- 20211007
LR  - 20231206
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 526
DP  - 2021 Apr 15
TI  - Developmental programming: Metabolic tissue-specific changes in endoplasmic 
      reticulum stress, mitochondrial oxidative and telomere length status induced by 
      prenatal testosterone excess in the female sheep.
PG  - 111207
LID - S0303-7207(21)00051-4 [pii]
LID - 10.1016/j.mce.2021.111207 [doi]
AB  - Prenatal testosterone (T) excess-induced metabolic dysfunctions involve tissue 
      specific changes in insulin sensitivity with insulin resistant, oxidative and 
      lipotoxic state in liver/muscle and insulin sensitive but inflammatory and 
      oxidative state in visceral adipose tissues (VAT). We hypothesized that 
      mitochondrial dysfunction, endoplasmic reticulum (ER) stress and premature 
      cellular senescence are contributors to the tissue-specific changes in insulin 
      sensitivity. Markers of mitochondrial number, function, and oxidative 
      phosphorylation (OxPhos), ER stress and cellular senescence (telomere length) 
      were assessed in liver, muscle and 4 adipose (VAT, subcutaneous [SAT], epicardiac 
      [ECAT] and perirenal [PRAT]) depots collected from control and prenatal T-treated 
      female sheep at 21 months of age. Prenatal T treatment led to: (a) reduction in 
      mitochondrial number and OxPhos complexes and increase in ER stress markers in 
      muscle; (b) increase in fibrosis with trend towards increase in short telomere 
      fragments in liver (c) depot-specific mitochondrial changes with OxPhos complexes 
      namely increase in SAT and reduction in PRAT and increase in mitochondrial number 
      in ECAT; (d) depot-specific ER stress marker changes with increase in VAT, 
      reduction in SAT, contrasting changes in ECAT and no changes in PRAT; and (d) 
      reduced shorter telomere fragments in SAT, ECAT and PRAT. These changes indicate 
      insulin resistance may be driven by mitochondrial and ER dysfunction in muscle, 
      fibrosis and premature senescence in liver, and depot-specific changes in 
      mitochondrial function and ER stress without involving cellular senescence in 
      adipose tissue. These findings provide mechanistic insights into pathophysiology 
      of metabolic dysfunction among female offspring from hyperandrogenic pregnancies.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Puttabyatappa, Muraly
AU  - Puttabyatappa M
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
FAU - Ciarelli, Joseph N
AU  - Ciarelli JN
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
FAU - Chatoff, Adam G
AU  - Chatoff AG
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
FAU - Padmanabhan, Vasantha
AU  - Padmanabhan V
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. Electronic 
      address: vasantha@umich.edu.
LA  - eng
GR  - P01 HD044232/HD/NICHD NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - P30 ES017885/ES/NIEHS NIH HHS/United States
GR  - R01 HD099096/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210217
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Messenger)
RN  - 3XMK78S47O (Testosterone)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Collagen/metabolism
MH  - Electron Transport
MH  - *Endoplasmic Reticulum Stress/genetics
MH  - Female
MH  - Fibrosis
MH  - Gene Dosage
MH  - Gene Expression Regulation
MH  - Liver/pathology
MH  - Mitochondria/*metabolism
MH  - Muscles/pathology
MH  - *Organ Specificity
MH  - Oxidation-Reduction
MH  - Oxidative Phosphorylation
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/genetics/*pathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Sheep
MH  - Telomere/*metabolism
MH  - Testosterone/*metabolism
PMC - PMC8005473
MID - NIHMS1674551
OTO - NOTNLM
OT  - ER stress
OT  - Insulin sensitivity
OT  - Metabolic tissues
OT  - Mitochondria
OT  - Oxidative stress
OT  - Telomere
EDAT- 2021/02/20 06:00
MHDA- 2021/10/08 06:00
PMCR- 2022/04/15
CRDT- 2021/02/19 20:11
PHST- 2020/11/09 00:00 [received]
PHST- 2021/02/02 00:00 [revised]
PHST- 2021/02/03 00:00 [accepted]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2021/10/08 06:00 [medline]
PHST- 2021/02/19 20:11 [entrez]
PHST- 2022/04/15 00:00 [pmc-release]
AID - S0303-7207(21)00051-4 [pii]
AID - 10.1016/j.mce.2021.111207 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2021 Apr 15;526:111207. doi: 10.1016/j.mce.2021.111207. Epub 
      2021 Feb 17.