Oral Presentation Society of Obstetric Medicine of Australia and New Zealand ASM 2015

Myo-inositol upregulates expression of the hexosamine signaling pathway in placenta (#9)

Marloes Dekker Nitert 1 2 , Leonie Callaway 1 2 , Helen Barrett 1 2
  1. School of Medicine, The University of Queensland, Herston, QLD, Australia
  2. UQ Centre for Clinical Research, The University of Queensland, Herston, QLD, Australia

Myo-inositol is an insulin-sensitising agent that in a limited number of studies has shown to improve fertility and prevent pregnancy complications in high-risk women. Myo-inositol is a common component of the diet mainly in vegetables and fruit. Myo-inositol is a structural component of the inositolphospates and the second messengers: phosphatidylinositol-phosphates (PIP). Myo-inositol supplementation could increase intracellular availability of PIP, which may result in upregulation of the hexosamine signaling pathway, which may drive cellular signaling toward protein synthesis and nutrient uptake. In the placenta, this may affect placental glucose uptake.

Aim: To investigate if supplementation with myo-inositol alters the placental expression of the hexosamine signaling pathway and glucose uptake.

Methods: Placental trophoblast BeWO cells were cultured for six days with and without 100 μM myo-inositol (n=7/condition). RNA was extracted, converted into cDNA and subjected to analysis with the Qiagen Human Insulin Resistance mini-array. Gene expression of the hexosamine signaling pathway enzymes GFAT, OGT1 and OGA as well as glucose transporters GLUT1 and GLUT3 were assessed with semi-quantitative real-time PCR analysis.

Results: 100 μM myo-inositol increased the mRNA expression of the O-GlcNAC transferase OGT by 3.5 fold from 0.90 (0.85-1.11) AU (median (IQR)) in control cells to 3.16 (2.8-4.18) AU (p<0.001) in myo-inositol cells. There were no significant differences in the expression of GFAT, OGA, GLUT1, GLUT3 or GLUT4.

Conclusion: Myo-inositol  upregulates the expression of OGT in trophoblast cells, potentially affecting cellular metabolism and the risk for developing complications of pregnancy. However, expression of glucose transporters is not affected by myo-inositol supplementation.