Placental mammalian target of rapamycin and related signaling pathways in an ovine model of intrauterine growth restriction.
OBJECTIVE
Both phosphorylated (p) mammalian target of rapamycin (mTOR) and protein S6 kinase 1 (p70S6K) are known to regulate protein synthesis and are affected during intrauterine growth restriction (IUGR). We studied the mTOR pathway during hyperthermia (HT)-induced IUGR in sheep.


METHODS
Beginning at 40 days gestational age, 4 ewes were exposed to HT for 55 days and 4 were exposed for 80 days to induce IUGR. Western blot analyses were performed for mTOR, p70S6K, 4E-binding protein 1, extracellularly regulated kinase (ERK), and AKT.


RESULTS
HT animals showed: smaller fetuses and placentas near term; reduced placental weight at midgestation; increased p-mTOR, p-ERK, and p-AKT; decreased p70S6K in the near-term cotyledons; decreased p- p70S6K; and increased p-ERK in the caruncles (maternal) near term.


CONCLUSIONS
Near-term IUGR ovine cotyledons showed up-regulation of p-mTOR, whereas p70S6K was decreased. This suggests that the changes in placental mTOR signaling proteins could be driven by the fetal stress observed near term in this model of IUGR.
Arroyo
Juan A
JA
Division of Perinatal Medicine, Department of Obstetrics and Gynecology, University of Colorado Denver and Health Sciences Center, Aurora, CO 80045, USA. juan.arroyo@ucdenver.edu
Brown
Laura D
LD
Galan
Henry L
HL
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005334:Fever; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D011494:Protein Kinases / Q000032:analysis* / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases