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Role of Reactive Oxygen Species in Gestational Diabetes and the Impact on the Developing Fetus

Graduate #32
Discipline: Biological Sciences
Subcategory: Physiology and Health

Diana Arriaga - California State University, Los Angeles
Co-Author(s): Melissa Cortes, California State University Los Angeles, Los Angeles,CA



Gestation diabetes mellites (GDM) is characterized by elevated levels of glucose in a pregnant woman’s bloodstream that occurs from an overproduction of hormones. Under GDM, elevated glucocorticoids (GC) and insulin like growth factor (IGF)-1 hormones in the placenta may possibly lead to an increase in the amount of reactive oxygen species (ROS) in the embryo due to an increase in glucose utilization and mitochondrial activity. Overproduction of ROS can modify the genome, thus predisposing offspring’s to diabetes and obesity later. The aim of the study is to investigate the mechanism by which GDM leads to an increased production of ROS and evaluate the epigenetic changes that occur. I hypothesize that under diabetic conditions, the embryo will have an increase in ROS production due to increased hormone levels, resulting in epigenetic changes in the offspring. An in vivo model for GDM will be established by feeding female mice a high-fat diet for four weeks. Controls will be fed a standard diet. Fasting blood glucose levels and glucose tolerance tests will monitor the development of diabetes. Mating between a diabetic or control female will occur with a normal male. At 6.5 and 17.5 days of gestation and 7 days post birth, maternal, fetal and placental blood and tissue will be collected. Biochemical assays will evaluate tissue ROS levels and epigenetic changes. Blood analysis will measure hormone and glucose levels. Results from this study will hopefully lead to the development of treatments to lower the incidence of diabetes in future generations.

Not Submitted

Funder Acknowledgement(s): The Louis Stokes Alliances for Minority Participation (LSAMP) program

Faculty Advisor: Dr. Katrina Yamazaki, Katrina.Yamazaki@calstatela.edu

Role: I have 70% of the work, sharing the other portion with the undergraduate student who is also part of the project. This entails doing most the work in the following techniques for our project. Cell culture and treatment of C2C12 myoblast cells. Western blot analysis to detect specific proteins in C2C12 myoblast cells using antibodies specific for GLUT1 to evaluate changes in the glucose transporter expression, iNOS to evaluate ROS production, OXPHOS to evaluate changes in the mitochondrial machinery and DNA methyltransferases to evaluate expression of proteins known to play a role in producing epigenetic changes. We will develop an animal model of GDM following approved procedures by the Institutional Animal Care and Use Committee at Cal State LA (currently under review).

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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