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

  • F. B. Fahlbusch (a1), A. Hartner (a1), C. Menendez-Castro (a1), S. C. Nögel (a1), I. Marek (a1), M. W. Beckmann (a2), E. Schleussner (a3), M. Ruebner (a2), H. Huebner (a2), H.-G. Dörr (a1), R. L. Schild (a4), J. Dötsch (a5) and W. Rascher (a1)...

Abstract

Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.

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Corresponding author

*Address for correspondence: F. B. Fahlbusch, MD, Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Loschgestr. 15, Erlangen 91054, Germany. (Email fabian.fahlbusch@uk-erlangen.de)

References

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

  • F. B. Fahlbusch (a1), A. Hartner (a1), C. Menendez-Castro (a1), S. C. Nögel (a1), I. Marek (a1), M. W. Beckmann (a2), E. Schleussner (a3), M. Ruebner (a2), H. Huebner (a2), H.-G. Dörr (a1), R. L. Schild (a4), J. Dötsch (a5) and W. Rascher (a1)...

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