Discipline: Biological Sciences
Subcategory: Physiology and Health
Melissa Cortes - California State University, Los Angeles
Co-Author(s): Diana Arriaga and Katrina Yamazaki, California State University, LA
Gestational diabetes mellitus (GDM) affects pregnant women and has increased significantly in recent years. During pregnancy, there is an increase in the production of the hormones, progesterone and placental lactogen, which are intended to help the growing embryo. However, the overproduction of these hormones can lead to GDM and be detrimental to the development of the embryo and subsequent fetus. Glucocorticoids (GC) and Insulin like Growth Factor (IGF)-1 are hormones that are upregulated as a result of GDM. In pregnant women, glucocorticoids help to ensure proper development and function of the placenta as well as regulate the functions of glucose transporters, GLUT1 and GLUT3. IGF-1’s role is to move glucose to insulin sensitive cells by binding to its IGF-1 receptor to decrease glucose levels in the blood and improve insulin sensitivity. The overexpression of GC and IGF-1 may lead to increases in reactive oxygen species (ROS) in the placenta due to increase glucose utilization and mitochondrial activity. The overproduction of ROS will lead to oxidative stress, which has the potential to modify the genome of the embryo. Therefore, we hypothesize that high levels of ROS present in a diabetic mother will induce epigenetic changes in the embryo causing the predisposition of diabetes and obesity in the offspring. An in vivo model will be used to test the hypothesis. Females will be placed on a high fat diet to induce diabetes. Control females will receive normal chow. Control and diabetic animals will be bred with a normal male. Offsprings will either be sacrificed at embryonic day 14, 17 or as an adult for tissue collection. Another group of females in this generation will be maintained on the high fat diet and bred again and tissue will be collected at the time points mentioned above. Tissue will be collected from each generation to determine if any epigenetic changes occurred. More specifically to determine if there is hypermethylation of DNA, histone modifications, or misregulation of microRNAs. Our anticipated results are that the increased presence of ROS in the mother will result in the offspring being born with higher levels of ROS than what is normal. This will correlate with epigenetic modifications, such as hypermethylation of DNA. More specifically we expect to see changes in the following genes: HAND1 & 2, T-Box, Nkx2.5-homeobox, and Pdx-1. Each of these genes play a different role in the development of the heart and any changes could lead to diabetic cardiomyopathy. This study will further help explain if the exposure to oxidative stress on the embryo will increase their risk of developing diabetes early on which can be detrimental because diabetics are already at a higher risk for developing cardiovascular disease.
Funder Acknowledgement(s): Louis Stokes Alliances for Minority Participation (LSAMP) Program, LSAMP Undergraduate Grant (HRD-1302873), NSF.
Faculty Advisor: Katrina Yamazaki, Katrina.Yamazaki@calstatela.edu
Role: With the help and guidance of my faculty mentor I along with another student equally worked on every aspect of this research. We began by developing a question and then forming the protocol for the procedure to eventually lead us to be able to perform it.