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Placental Mammalian Target of Rapamycin and Related Signaling Pathways in an Ovine Model of Intrauterine Growth Restriction

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Publisher Elsevier
Date 2009 Oct 6
PMID 19800600
Citations 21
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Abstract

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.

Study Design: 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.

Conclusion: 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.

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