Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

THE PROBLEM is that 1 in 25 women will develop glucose intolerance, or diabetes mellitus (DM)-like state during pregnancy. This increases the risk to the baby, as well as for obesity and type 2 DM (needing insulin) in later life. WHAT'S GOING ON? There is certainly a genetic component as some ethnic groups are at increased risk, but it is unclear why some pregnant women who develop DM release less insulin than is needed. Human (h) placental hormones, including placental lactogen (CS) and placental growth hormone (GH-V), help to increase the number of insulin-producing pancreatic cells, but CS/GH-V production is also affected by glucose and insulin levels. Thus, changes in CS/GH-V production may contribute to DM. WE BELIEVE that the food we eat can both affect the placental environment, and use of our genetic material, DNA, and therefore the genes that code for proteins, including CS and GH-V. This happens in part by (epigenetic) changes in levels of small nucleic acids (non-coding RNAs) used to switch genes "on" or "off" during pregnancy. These modifications may contribute to, or worsen DM in pregnancy. They may also reflect "tracks" left by changes to the environment that can be "followed" for monitoring and deciding on any treatment. The study of the human CS/GH-V genes is problematic, however, because it is difficult to take placenta samples during pregnancy, and the GH-V gene is only found in humans and other primates. AS A SOLUTION we made mice containing the human CS/GH-V genes, which will be fed a high fat diet in pregnancy to create a DM-like state. The effect on changes to the "on/off" status of the CS/GH-V genes will be studied. The equivalent "changes" will also be tested in human blood and placental samples from overweight women diagnosed with DM to help prioritize the "changes" to be studied further. WE HOPE to learn more about how this disease progresses, identify markers and develop a "humanized" mouse model to begin to assess possible treatments.