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

Published online by Cambridge University Press:  20 May 2015

F. B. Fahlbusch*
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
A. Hartner
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
C. Menendez-Castro
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
S. C. Nögel
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
I. Marek
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
M. W. Beckmann
Affiliation:
Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany
E. Schleussner
Affiliation:
Department of Gynecology and Obstetrics, University of Jena, Jena, Germany
M. Ruebner
Affiliation:
Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany
H. Huebner
Affiliation:
Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany
H.-G. Dörr
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
R. L. Schild
Affiliation:
Department of Obstetrics & Gynecology, Diakonische Dienste Hannover, Hannover, Germany
J. Dötsch
Affiliation:
Childrens’ and Adolescents’ Hospital, University of Cologne, Cologne, Germany
W. Rascher
Affiliation:
Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany
*
*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)

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.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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