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The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?

F B Fahlbusch1, A Hartner1, C Menendez-Castro1

  • 11Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.

Journal of Developmental Origins of Health and Disease
|May 21, 2015
PubMed

Insights

Idiopathic intrauterine growth restriction (IUGR) is linked to placental nutrient issues. Activated mammalian target of rapamycin (mTOR) in the placenta correlates with catch-up growth in infants with IUGR.

Area of Science:

  • Reproductive Biology
  • Developmental Biology
  • Metabolic Research

Background:

  • Idiopathic intrauterine growth restriction (IUGR) stems from insufficient placental nutrient supply.
  • Infants with IUGR who experience postnatal catch-up growth face increased risks of adult cardiovascular and metabolic diseases.
  • The mammalian target of rapamycin (mTOR) pathway is recognized as a placental nutrient sensor.

Purpose of the Study:

  • To investigate correlations between placental mTOR signaling pathway components and postnatal growth parameters in infants with IUGR.
  • To analyze the expression and activity of key mTOR pathway proteins (Akt, AMPKα, mTOR, p70S6K1, IRS-1) in IUGR versus appropriate-for-gestational age (AGA) placentas.
  • To correlate placental mTOR pathway signaling with auxological data at birth and one year of age.

Main Methods:

  • Western blotting was used to assess protein expression and activity of mTOR pathway components in IUGR and AGA placentas.
  • Immunohistochemistry was employed to detect mTOR localization within placental tissues.
  • Retrospective auxological follow-up data at one year of age were analyzed and correlated with placental findings.

Main Results:

  • Significant catch-up growth was observed in the IUGR group during the first year of life.
  • Activated mTOR was detected in various placental compartments via immunohistochemistry.
  • Correlations were identified between placental mTOR pathway signaling components and auxological data at birth and one year in IUGR infants.
  • No pathognomonic changes in protein expression or phosphorylation of mTOR pathway components were found in postpartum IUGR versus AGA placentas.

Conclusions:

  • The level of activated placental mTOR correlates with early catch-up growth in infants following IUGR.
  • The complexity and cellular distribution of mTOR signaling limit its utility as a predictive biomarker for IUGR outcomes.
  • Further research is needed to fully elucidate the role of mTOR in placental function and infant development.

Keywords:
IUGRmTORplacentapostnatal development

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