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Updated: Aug 7, 2026

The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo
Published on: August 2, 2017
mTOR: a placental growth signaling sensor
H Y Wen1, S Abbasi, R E Kellems
1Department of Biochemistry and Molecular Biology, University of Texas, Houston Medical School, Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
Growth factors and nutrients regulate placental development by controlling trophoblast cell proliferation. This study reveals how angiopoietin-2 and glucose activate mammalian target of rapamycin (mTOR) signaling, highlighting mTOR
Area of Science:
- Cell Biology
- Biochemistry
- Reproductive Biology
Background:
- Trophoblast cell proliferation and differentiation are crucial for placental development, influenced by hormones, growth factors, and nutrient availability.
- Intracellular signaling pathways mediating these effects on trophoblast cells remain incompletely understood.
Purpose of the Study:
- To investigate the signaling pathways regulating trophoblast proliferation in response to angiopoietin-2 (Ang-2) and glucose.
- To elucidate the roles of phosphatidylinositol-3 (PI-3) kinase, mammalian target of rapamycin (mTOR), and glutamine fructose-6-phosphate amidotransferase (GFAT) in nutrient and growth factor signaling.
Main Methods:
- Utilized immortalized human trophoblast cells (HTR-8/SVneo).
- Investigated signaling pathways including PI-3 kinase, mTOR, and GFAT in response to Ang-2 and glucose.
- Analyzed the upstream regulation of mTOR by growth factors and nutrients.
Main Results:
- Angiopoietin-2 (Ang-2) induced trophoblast proliferation via PI-3 kinase and mTOR activation.
- Glucose stimulated trophoblast proliferation through mTOR, independent of PI-3 kinase, involving GFAT as a novel nutrient sensor.
- GFAT metabolites acted upstream of mTOR, linking nutrient sensing to trophoblast cell proliferation.
Conclusions:
- Growth factor and nutrient signaling converge at tuberin, an upstream regulator of mTOR.
- mTOR serves as a critical signaling sensor for placental growth.
- This study establishes a novel link between mTOR, GFAT metabolites, and nutrient sensing in trophoblast cell proliferation.
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