Placental mammalian target of rapamycin and related signaling pathways in an ovine model of intrauterine growth restriction.

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.

journal_name

Am J Obstet Gynecol

authors

Arroyo JA,Brown LD,Galan HL

doi

10.1016/j.ajog.2009.07.031

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

616.e1-7

issue

6

eissn

0002-9378

issn

1097-6868

pii

S0002-9378(09)00818-7

journal_volume

201

pub_type

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