PMID- 26660559
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151215
LR  - 20210109
IS  - 2051-817X (Print)
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 3
IP  - 12
DP  - 2015 Dec
TI  - Hypoxia reduces placental mTOR activation in a hypoxia-induced model of 
      intrauterine growth restriction (IUGR).
LID - 10.14814/phy2.12651 [doi]
LID - e12651
AB  - Mammalian target of rapamycin (mTOR) is a protein that regulates cell growth in 
      response to altered nutrient and growth factor availability. Our objective was to 
      assess activated mTOR and its intracellular intermediates p70, and 4EBP1 in 
      placental and invasive trophoblast cells in a hypoxia-induced model of 
      intrauterine growth restriction (IUGR) in rats. Rats were treated with hypoxia 
      (9%) for 4 days. Placental and fetal weights, as well as conceptus numbers were 
      recorded at the time of necropsy. Immunohistochemistry was used to determine the 
      level of trophoblast invasion and apoptosis. Western blots were used to determine 
      the activation of mTOR, p70, and 4EBP1 in the placenta and the uterine 
      mesometrial compartment. We observed (1) decreased placental (21%) and fetal 
      (24%) weights (P < 0.05); (2) decreased trophoblast invasion; (3) significantly 
      increased active 4EBP1 (28%; P < 0.05) in invasive trophoblast cells yet no 
      changes in the activation of mTOR and p70 proteins; and (4) a significant 
      decrease in the activation of mTOR (48%; P < 0.05) with no differences in p70 or 
      4EBP1 activation in the placenta. We conclude that the development of IUGR is 
      correlated with decreased activation of the mTOR protein in the placenta and 
      increased 4EBP1 activity in the invading trophoblast. These results provide 
      important insight into the physiological relevance of these pathways. 
      Furthermore, modification of these and other related targets during gestation may 
      alleviate IUGR severity.
CI  - (c) 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of the American Physiological Society and The Physiological Society.
FAU - Kimball, Rebecca
AU  - Kimball R
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah.
FAU - Wayment, Montana
AU  - Wayment M
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah.
FAU - Merrill, Daniel
AU  - Merrill D
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah.
FAU - Wahlquist, Tyler
AU  - Wahlquist T
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah.
FAU - Reynolds, Paul R
AU  - Reynolds PR
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah.
FAU - Arroyo, Juan A
AU  - Arroyo JA
AD  - Lung and Placenta Research Laboratory, , Physiology and Developmental Biology, 
      Brigham Young University, Provo, Utah jarroyo@byu.edu.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
PMC - PMC4760431
OTO - NOTNLM
OT  - Hypoxia
OT  - IUGR
OT  - mTOR
OT  - placenta
OT  - trophoblast
EDAT- 2015/12/15 06:00
MHDA- 2015/12/15 06:01
PMCR- 2015/12/10
CRDT- 2015/12/15 06:00
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2015/12/15 06:01 [medline]
PHST- 2015/12/10 00:00 [pmc-release]
AID - 3/12/e12651 [pii]
AID - PHY212651 [pii]
AID - 10.14814/phy2.12651 [doi]
PST - ppublish
SO  - Physiol Rep. 2015 Dec;3(12):e12651. doi: 10.14814/phy2.12651.