Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of developmental origins of health and disease, 2015-08, Vol.6 (4), p.317-326

Ort / Verlag

Cambridge, UK: Cambridge University Press

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.