title: The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?
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.
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: F B
authors.initials: FB
authors.lastname: Fahlbusch
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hartner
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: C
authors.initials: C
authors.lastname: Menendez-Castro
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: S C
authors.initials: SC
authors.lastname: Nögel
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: I
authors.initials: I
authors.lastname: Marek
authors.affiliation: 2Department of Gynecology and Obstetrics,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Beckmann
authors.affiliation: 3Department of Gynecology and Obstetrics,University of Jena,Jena,Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schleussner
authors.affiliation: 2Department of Gynecology and Obstetrics,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ruebner
authors.affiliation: 2Department of Gynecology and Obstetrics,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: H
authors.initials: H
authors.lastname: Huebner
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: H-G
authors.initials: HG
authors.lastname: Dörr
authors.affiliation: 4Department of Obstetrics & Gynecology,Diakonische Dienste Hannover,Hannover,Germany.
authors.forename: R L
authors.initials: RL
authors.lastname: Schild
authors.affiliation: 5Childrens' and Adolescents' Hospital,University of Cologne,Cologne,Germany.
authors.forename: J
authors.initials: J
authors.lastname: Dötsch
authors.affiliation: 1Department of Pediatrics and Adolescent Medicine,University of Erlangen-Nürnberg,Erlangen,Germany.
authors.forename: W
authors.initials: W
authors.lastname: Rascher
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D016022:Case-Control Studies; D002657:Child Development / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D055372:AMP-Activated Protein Kinases
keywords: IUGR; mTOR; placenta; postnatal development