The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?. (20th May 2015)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Journal of developmental origins of health and disease. Volume 6:Number 4(2015)
• Page Start: 317
• Page End: 326
• Publication Date: 2015-05-20
• Subjects: IUGR, -- mTOR, -- placenta, -- postnatal development; Developmental biology -- Periodicals; Embryology, Human -- Periodicals; Disease susceptibility -- Periodicals; Prenatal influences -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; 612.64
• DOI: 10.1017/S2040174415001154
• Languages: English
• ISSNs: 2040-1744

Abstract

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.