mTOR, placenta, gestational diabetes mellitus, intrauterine growth restriction, preeclampsia


The mechanistic target of rapamycin (mTOR) pathway is involved in placental growth and function during pregnancy. The mTOR pathway responds to nutrient availability and growth factors regulating protein transcription and cell growth. mTOR disruptions are associated with the development of obstetric complications which may result in adverse health outcomes for the mother and/or fetus. The purpose of this study is to identify the differing placental expression of various mTOR-associated proteins during normal gestation (Control), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Immunohistochemistry was used to stain human placenta for activated proteins (phospho; p)AKT, (p)ERK, (p)mTOR, (p)p70 and (p)4EBP1. Real-time PCR array was completed to show differing placental expression of additional mTOR-associated genes during these conditions. We observed: 1) increased (p)AKT during GDM, 2) increased (p)ERK during IUGR, 3) increased (p)mTOR during GDM, while decreased during IUGR and PE, 4) increased (p)p70 during IUGR while decreased during GDM and PE, 5) increased (p)4EBP1 during GDM, IUGR, and PE, and 6) differential placental expression of mTOR pathway associated genes. We conclude that diverse regulation of the mTOR pathway is uniquely involved in the development of the obstetric complications studied. These results may provide insights into the physiological relevance of these pathways, and if so, their modification during gestation may help alleviate these diseases.

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Life Sciences


Physiology and Developmental Biology

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