Department of Obstetrics and Gynecology
Washington University School of Medicine
Dr. Riley studied TRAIL/Receptor expression and its role in murine blastocyst apoptosis. Women with poorly controlled diabetes have a higher incidence of early pregnancy complications. Dr. Riley found that both TRAIL and its receptor KILLER (MK) are expressed from the 1-cell through the blastocyst stage of embryo development. To determine whether maternal diabetes sensitizes blastocysts to TRAIL-induced apoptosis female mice were made diabetic via a single intraperitoneal injection of streptozotocin. The mice were then superovulated, mated and blastocysts were harvested. Blastocysts derived from diabetic mice treated with recombinant murine TRAIL in vitro were significantly more apoptotic than either untreated diabetic blastocysts or control blastocysts with or without TRAIL treatment. These data demonstrated the presence of TRAIL and MK, a death-inducing ligand and its receptor, on mammalian preimplantation embryos and that high glucose sensitizes blastocysts to TRAIL-induced apoptosis. Dr. Riley has 17 publications (seven first author) from her training with Dr. Moley. She received the following funding after her support on this K12 that included a Diabetes Research Training Center (DRTC, now DRC) Pilot and Feasibility grant, and a grant through the Center of Nutrition. Dr. Riley is currently an Assistant Professor in Obstetrics and Gynecology at Washington University.
BIRCWH Scholar from 08/01/2006 until 07/31/2011
Women with insulin-resistance, obesity and type II diabetes experience adverse pregnancy outcomes including congenial malformations and first trimester pregnancy loss. Hyperglycemia is responsible in part, however, exposure to high glucose concentrations in vitro does not replicate the in vivo condition. Recent studies have revealed that fructose levels are 50% higher in diabetic patients as compared to controls, and several other reports have demonstrated that serum fructose levels are a factor in the progression of diabetic complications. We propose that elevated fructose levels in type II diabetic women have a detrimental effect on preimplantation embryos and that fructose plays a significant role in the complications associated with diabetic pregnancies. Our objective is to determine whether high fructose concentrations adversely affect preimplantation development and embryo competence. In addition we will determine the mechanism(s) by which high fructose mediates these effects.
The rationale for this investigation is that if high fructose concentrations lead to poor embryo outcome then the use of anti-oxidants or an aldose reductase inhibitor may improve embryo development during the preimplantation period and subsequent pregnancy outcome.
We hypothesize that embryos exposed to high fructose will become apoptotic, insulin-resistant and display increased flux through the glycolytic pathway. High fructose will likely decrease embryo competence that is to say we expect to find increased numbers of resorptions and malformations among embryos exposed to high fructose. We also hypothesize that the mechanism by which high fructose levels induce adverse effects on embryos involves increased production of reactive oxygen species and increased flux through the polyol pathway.
1.How do blastocysts utilize fructose?
2.Do high fructose concentrations lead to adverse effects on blastocysts and problems with embryo competence? What mechanisms are responsible for the harmful effects?
3.Using gene chip technology can we identify genes that are differentially expressed in embryos exposed to high fructose?