Joan K. Riley, Ph.D.
Abstract
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.
Hypothesis
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.
Specific Aims
- How do blastocysts utilize fructose?
- Do high fructose concentrations lead to adverse effects on blastocysts and problems with embryo competence? What mechanisms are responsible for the harmful effects?
- Using gene chip technology can we identify genes that are differentially expressed in embryos exposed to high fructose?
