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

• Published in: Journal of developmental origins of health and disease Vol. 6; no. 4; pp. 317 - 326
• Main 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.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.08.2015
• Subjects: AMP-Activated Protein Kinases - metabolism; Cardiovascular disease; Case-Control Studies; Child Development - physiology; Female; Fetal Growth Retardation - metabolism; Humans; Infant; Infant, Newborn; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Insulin-like growth factors; Kinases; Obesity; Original Article; Physical growth; Placenta - metabolism; Pregnancy; Proto-Oncogene Proteins c-akt - metabolism; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; mTOR; placenta; IUGR; postnatal development
• ISSN: 2040-1744; 2040-1752
• DOI: 10.1017/S2040174415001154

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.