Xuemei Zhang

The impact of metformin on early placental development and metabolism

Metformin has been variously proposed as a potential anti-ageing anti-inflammatory, or anti-cancer drug in addition to its major use in diabetes therapy. Metformin crosses the placenta, most likely via a variety of organic cation transporters, and our recent work shows that this results in positive linear correlations between maternal, placental, and fetal concentrations, at a maternal:fetal ratio of ~1:1.5.We therefore hypothese that metformin protects the placenta during EVT differentiation from the effects of exposure to excess oxygen by preventing oxygen conversion to ROS. And metformin promotes NOTCH1 signaling via AMPK leading to increased EVT differentiation and invasion. Metformin reduces early placental ATP production and does so to a greater extent at lower glucose concentrations.

So we want to test these hypotheses as follows:

(1)To determine whether metformin exposure promotes differentiation and invasion of EVT
(2)To determine the effects of metformin on oxidative phosphorylation and subsequently oxidative stress in trophoblast under different ambient oxygen concentrations 
(3)To determine how glycolysis, cellular metabolism, and ATP production in trophoblast are affected by metformin in varying extracellular glucose concentrations