PMID- 30124960
OWN - NLM
STAT- MEDLINE
DCOM- 20191212
LR  - 20211204
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 104
IP  - 2
DP  - 2019 Feb 1
TI  - IUGR Is Associated With Marked Hyperphosphorylation of Decidual and Maternal 
      Plasma IGFBP-1.
PG  - 408-422
LID - 10.1210/jc.2018-00820 [doi]
AB  - CONTEXT: The mechanisms underpinning intrauterine growth restriction (IUGR), as a 
      result of placental insufficiency, remain poorly understood, no specific 
      treatment is available, and clinically useful biomarkers for early detection are 
      lacking. OBJECTIVE: We hypothesized that human IUGR is associated with inhibition 
      of mechanistic target of rapamycin (mTOR) and activation of amino acid response 
      (AAR) signaling, increased protein kinase casein kinase-2 (CK2) activity, and 
      increased insulin-like growth factor-binding protein 1 (IGFBP-1) expression and 
      phosphorylation in decidua and that maternal plasma IGFBP-1 hyperphosphorylation 
      in the first trimester predicts later development of IUGR. DESIGN, SETTING, AND 
      PARTICIPANTS: Decidua [n = 16 appropriate-for-gestational age (AGA); n = 16 IUGR] 
      and maternal plasma (n = 13 AGA; n = 13 IUGR) were collected at delivery from two 
      different cohorts. In addition, maternal plasma was obtained in the late first 
      trimester from a third cohort of women (n = 7) who later delivered an AGA or IUGR 
      infant. MAIN OUTCOME MEASURES: Total IGFBP-1 expression and phosphorylation 
      (Ser101/Ser119/Ser169), mTOR, AAR, and CK2 activity in decidua and IGFBP-1 
      concentration and phosphorylation in maternal plasma. RESULTS: We show that 
      decidual IGFBP-1 expression and phosphorylation are increased, mTOR is markedly 
      inhibited, and AAR and CK2 are activated in IUGR. Moreover, IGFBP-1 
      hyperphosphorylation in first-trimester maternal plasma is associated with the 
      development of IUGR. CONCLUSIONS: These data are consistent with the possibility 
      that the decidua functions as a nutrient sensor linking limited oxygen and 
      nutrient availability to increased IGFBP-1 phosphorylation, possibly mediated by 
      mTOR and AAR signaling. IGFBP-1 hyperphosphorylation in first-trimester maternal 
      plasma may serve as a predictive IUGR biomarker, allowing early intervention.
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 - Abu Shehab, Majida
AU  - Abu Shehab M
AD  - Department of Pediatrics, University of Western Ontario, London, Ontario, Canada.
FAU - Nygard, Karen
AU  - Nygard K
AD  - Biotron Laboratory, University of Western Ontario, London, Ontario, Canada.
FAU - Biggar, Kyle
AU  - Biggar K
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.
FAU - Singal, Sahil S
AU  - Singal SS
AD  - Department of Biochemistry, University of Western Ontario, London, Ontario, 
      Canada.
FAU - Santoro, Nanette
AU  - Santoro N
AD  - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, 
      University of Colorado Anschutz Medical Campus, Aurora, Colorado.
FAU - Powell, Theresa L
AU  - Powell TL
AD  - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, 
      University of Colorado Anschutz Medical Campus, Aurora, Colorado.
AD  - Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, 
      Colorado.
FAU - Jansson, Thomas
AU  - Jansson T
AD  - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, 
      University of Colorado Anschutz Medical Campus, Aurora, Colorado.
LA  - eng
GR  - R01 HD089980/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Biomarkers)
RN  - 0 (IGFBP1 protein, human)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood/metabolism
MH  - Cohort Studies
MH  - Decidua/*metabolism/pathology
MH  - Female
MH  - Fetal Growth Retardation/blood/*diagnosis/metabolism
MH  - Humans
MH  - Infant, Low Birth Weight
MH  - Infant, Newborn
MH  - Insulin-Like Growth Factor Binding Protein 1/blood/*metabolism
MH  - Male
MH  - Phosphorylation
MH  - Pregnancy
MH  - Pregnancy Trimester, First
MH  - Prognosis
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Young Adult
PMC - PMC6306389
EDAT- 2018/08/21 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/08/16
CRDT- 2018/08/21 06:00
PHST- 2018/04/15 00:00 [received]
PHST- 2018/08/13 00:00 [accepted]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/08/21 06:00 [entrez]
PHST- 2019/08/16 00:00 [pmc-release]
AID - 5075151 [pii]
AID - jcem_201800820 [pii]
AID - 10.1210/jc.2018-00820 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2019 Feb 1;104(2):408-422. doi: 10.1210/jc.2018-00820.