Endometrial function in women with diabetes – role of Hexosamine Biosynthetic Pathway
Professor Melissa Westwood and her team aim to find out how high glucose levels cause problems in the womb that reduce fertility in women with diabetes. Their findings will support the development of new therapies to diagnose and correct these problems.
Background to research
Diabetes has a significant impact on female reproductive health, especially if glucose levels are outside ideal ranges.
Many women with diabetes have issues with fertility, due to problems with the endometrium (the lining of the womb), which make it less receptive to an embryo and reduce its ability to detect whether an embryo is healthy. This can lead to difficulties conceiving, or result in miscarriages during the first trimester of pregnancy, which can be devastating for women and their families.
Studies in animals show that high glucose levels cause the womb to function incorrectly, but the underlying mechanisms involved are unclear.
Other organs that sense glucose levels do so by tagging proteins inside cells with a sugar molecule called O-GlcNAc, which leads to changes in cell function. Dr Melissa Westwood and her team have found that the womb has the chemical machinery needed to add or remove O-GlcNAc tags.
Professor Westwood and her team aim to find out how high glucose levels cause problems in the womb and uncover ways of diagnosing and correcting them in women with diabetes.
They will do this by studying the impact of O-GlcNAc tags on the ability of the womb to accept embryos. This will involve altering the efficiency of the tagging process, or by exposing cells from the womb to different levels of glucose, insulin or metformin to mimic the conditions seen in women with diabetes.
The researchers will also find out exactly which proteins get tagged by O-GlcNAc, to uncover the reasons why the womb doesn't function properly when glucose levels are high.
In addition, they'll study embryo implantation in the lab by combining cells that resemble the womb surface with embryos from mice and humans, and monitor them under the microscope.
Potential benefit to people with diabetes
Findings from this research could have an immediate impact on our understanding of how high glucose levels affect the function of the womb, hopefully helping to solve fertility problems in women with diabetes. The results will also support the development of new therapies to help women with diabetes have successful pregnancies.