PMID- 30476008
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20211204
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 100
IP  - 4
DP  - 2019 Apr 1
TI  - Novel roles of mechanistic target of rapamycin signaling in regulating fetal 
      growthdagger.
PG  - 872-884
LID - 10.1093/biolre/ioy249 [doi]
AB  - Mechanistic target of rapamycin (mTOR) signaling functions as a central regulator 
      of cellular metabolism, growth, and survival in response to hormones, growth 
      factors, nutrients, energy, and stress signals. Mechanistic TOR is therefore 
      critical for the growth of most fetal organs, and global mTOR deletion is 
      embryonic lethal. This review discusses emerging evidence suggesting that mTOR 
      signaling also has a role as a critical hub in the overall homeostatic control of 
      fetal growth, adjusting the fetal growth trajectory according to the ability of 
      the maternal supply line to support fetal growth. In the fetus, liver mTOR 
      governs the secretion and phosphorylation of insulin-like growth factor binding 
      protein 1 (IGFBP-1) thereby controlling the bioavailability of insulin-like 
      growth factors (IGF-I and IGF-II), which function as important growth hormones 
      during fetal life. In the placenta, mTOR responds to a large number of 
      growth-related signals, including amino acids, glucose, oxygen, folate, and 
      growth factors, to regulate trophoblast mitochondrial respiration, nutrient 
      transport, and protein synthesis, thereby influencing fetal growth. In the 
      maternal compartment, mTOR is an integral part of a decidual nutrient sensor 
      which links oxygen and nutrient availability to the phosphorylation of IGFBP-1 
      with preferential effects on the bioavailability of IGF-I in the maternal-fetal 
      interface and in the maternal circulation. These new roles of mTOR signaling in 
      the regulation fetal growth will help us better understand the molecular 
      underpinnings of abnormal fetal growth, such as intrauterine growth restriction 
      and fetal overgrowth, and may represent novel avenues for diagnostics and 
      intervention in important pregnancy complications.
CI  - (c) The Author(s) 2018. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction.
FAU - Gupta, Madhulika B
AU  - Gupta MB
AD  - Department of Pediatrics, University of Western Ontario, London, Ontario, Canada.
AD  - Department of Biochemistry, University of Western Ontario, London, Ontario, 
      Canada.
AD  - Children's Health Research Institute, London, Ontario, Canada.
FAU - Jansson, Thomas
AU  - Jansson T
AD  - Department of Obstetrics and Gynecology, Division of Reproductive Sciences, 
      University of Colorado | Anschutz Medical Campus, Aurora, Colorado, USA.
LA  - eng
GR  - R01 HD065007/HD/NICHD NIH HHS/United States
GR  - R01 HD068370/HD/NICHD NIH HHS/United States
GR  - P01 HD021350/HD/NICHD NIH HHS/United States
GR  - R01 HD089980/HD/NICHD NIH HHS/United States
GR  - R01 HD078376/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetal Development/*genetics
MH  - Fetal Growth Retardation/genetics/metabolism
MH  - Fetal Macrosomia/genetics/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Placenta/metabolism
MH  - Pregnancy
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/genetics/*physiology
PMC - PMC6698747
OTO - NOTNLM
OT  - decidua
OT  - developmental origins of health and disease
OT  - fetal development
OT  - insulin-like growth factor
OT  - intrauterine growth restriction
OT  - kinases
OT  - metabolism
OT  - nutrition
OT  - placenta
OT  - placental transport
OT  - pregnancy
OT  - syncytiotrophoblast
EDAT- 2018/11/27 06:00
MHDA- 2020/06/02 06:00
PMCR- 2020/04/01
CRDT- 2018/11/27 06:00
PHST- 2018/09/12 00:00 [received]
PHST- 2018/11/08 00:00 [revised]
PHST- 2018/11/19 00:00 [accepted]
PHST- 2018/11/27 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2018/11/27 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - 5195511 [pii]
AID - ioy249 [pii]
AID - 10.1093/biolre/ioy249 [doi]
PST - ppublish
SO  - Biol Reprod. 2019 Apr 1;100(4):872-884. doi: 10.1093/biolre/ioy249.