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

Fahlbusch FB, Menendez-Castro C, Nögel S, Marek I, Beckmann M, Schleussner E, Ruebner M, Huebner H, Dörr HG, Schild RL, Doetsch J, Rascher W, Hartner A (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 6

Pages Range: 317-26

Journal Issue: 4

DOI: 10.1017/S2040174415001154

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 ?, 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.

Authors with CRIS profile

Involved external institutions

Friedrich-Schiller-Universität Jena Germany (DE) DIAKOVERE gGmbH (Diakonische Dienste Hannover (DDH)) Germany (DE) Universität zu Köln Germany (DE)

How to cite

APA:

Fahlbusch, F.B., Menendez-Castro, C., Nögel, S., Marek, I., Beckmann, M., Schleussner, E.,... Hartner, A. (2015). The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction? Journal of Developmental Origins of Health and Disease, 6(4), 317-26. https://dx.doi.org/10.1017/S2040174415001154

MLA:

Fahlbusch, F. B., et al. "The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?" Journal of Developmental Origins of Health and Disease 6.4 (2015): 317-26.

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