Investigators: A/Professor Guiying Nie (1), Dr Sarah Paule (1), A/Prof Luk Rombauts (2,3), A/Prof Beverley Vollenhoven (2,3)
1 Hudson Institute of Medical Research, Clayton; 2 Monash IVF, Clayton; 3 Monash Dept Obstetrics and Gynaecology, Clayton
Assisted reproductive technology has progressed into an important medical intervention to overcome infertility. However, although embryo culture/selection/transfer techniques have advanced greatly, implantation failure still poses a crucial limiting factor. It is believed that the problem is the “soil for the seeds”, the endometrium. For implantation to occur, the endometrium must differentiate into a receptive state which is primarily driven by the ovarian hormones estrogen and progesterone. As the embryo first contacts the surface of the endometrial epithelium, this surface must become adhesive for embryo attachment. Although it is known that the endometrial epithelium remodels structurally and functionally to gain receptivity, the exact molecular changes are not well understood.
Our previous proteomics studies with the support of Monash IVF have identified a number of molecules that are drastically altered in the endometrial epithelium for receptivity; one of which is an anti-adhesive molecule called podocalyxin. It is a large and extensively O-glycosylated sialomucin of type 1 transmembrane protein. Podocalyxin was not previously reported in the human endometrium but known to regulate both adhesion and cell morphology in other systems. Our preliminary data strongly suggest that podocalyxin is an anti-adhesive molecule presented on the apical surface of endometrial epithelium and that endometrial receptivity is accompanied by podocalyxin removal. We aim to prove that podocalyxin is an important and previously unknown barrier of endometrial receptivity and failure of podocalyxin removal is associated with endometrial infertility.