Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
In humans, the natural rate of conception is about 30%, with most failed pregnancies due to implantation failure. In fact, successful implantation depends on the synchronized development and cross-talk among embryos, endometrial epithelial and stromal cells. Expressions of certain surface protein markers during the secretory phase of the endometrium is crucial for successful implantation of the embryo. We recently used a proteomic approach to compare surface proteins expressed in human endometrial (receptive: Ishikawa and non-receptive: AN3CA) epithelial cell lines and identified Protein Disulfide-Isomerase (PDI) as one of the surface proteins that were highly expressed in non-receptive endometrial AN3CA cells. PDI is a soluble 55-kDa protein mainly located in the endoplasmic reticulum and functions to maintain an oxidative environment. However, cell membrane PDI mainly acts as a reductase. Interestingly, PDI binds to b3 integrin to regulate endothelial and platelet functions. Importantly, b3 integrin was highly expressed in receptive endometrium during the ‘window of implantation’ and down-regulated in women with unexplained recurrent pregnancy loss.
We hypothesize that the receptivity of endometrial epithelial cells is regulated by steroid hormones involved in membrane localization of PDI, which in turn regulates b3 integrin function for spheroid/embryo attachment. Therefore, we propose (1) to study the effect of steroid hormones on the expression and membrane localization of PDI and on spheroid attachment, (2) to investigate the role of PDI on b3 integrin activity and bisulfide bond formation in regulating spheroid attachment; and (3) to investigate the expression of PDI and/or b3 integrin in endometrial epithelial cells as surface markers to predict implantation and pregnancy in clinical IVF. Results from this study will give us a better understanding of the role of PDI and b3 integrin proteins for embryo attachment, and whether PDI and 3 integrin can be used as predictors of implantation and pregnancy in clinical IVF.
Dr CKF Lee, Department of Obstetrics and Gynaecology
Dr. Lee got his Ph.D. in Biochemistry from the Chinese University of Hong Kong and trained in postdoctoral training at Tufts University, Massachusetts, USA. He joined the Department of Obstetrics and Gynaecology at The University of Hong Kong as a Research Assistant Professor in 1998 and was promoted to Associate Professor in 2008. He was Past-President of the Hong Kong Society for Reproductive Medicine, and the Hong Kong Society of Endocrinology, Metabolism, and Reproduction. He has published more than 90 original articles in international journals with an H index of 32 (total citation >3000). His students have obtained many international and local awards including ‘The Best Poster Award of Society for the Study of Reproduction (SSR) – Southeast Asia Region’.
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