Project Leaders

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Proteomic analysis of uterine fluid: biomarker discovery program

Using state-of-the-art proteomics, glycoproteomics and multiplex analyses, we are identifying the proteins in the uterine cavity throughout the menstrual cycle and in women with infertility and other endometrial disorders. We validate selected proteins by Western blot while immunohistochemistry establishes the cellular sources. Functional studies of selected proteins are performed in our established human ex-vivo and in vitro models.

Implantation can only occur during a three- to four- day period in the mid-secretory phase of a woman’s menstrual cycle. The epithelial cells lining the uterine cavity become highly secretory during endometrial receptivity. Secreted products released into the uterine cavity act on both the endometrium and the embryo to facilitate successful implantation.

At this time, there is no way of testing whether a woman’s endometrium will become receptive in any cycle. We are addressing this issue to improve success rates of IVF and assist women with endometrial-based infertility.

We are analysing endometrial secreted proteins in uterine fluid to assist in the detection of biologically relevant proteins useful as biomarkers for uterine receptivity. We have already identified cohorts of proteins and glycoprotein isoforms, previously unknown to be components of uterine fluid, which alter with cycle phase and fertility status. Selected fingerprints of these proteins are showing considerable promise as biomarkers and a substantial trial in women undergoing IVF is underway.

Functions of components of uterine fluid: potential targets for alleviating infertility

The first steps of embryo implantation occur within the uterine cavity where both the trophectoderm (the outer cells of the embryo that later become part of the placenta) and the endometrial epithelium must undergo molecular and structural changes essential for successful implantation. We are establishing functions of various molecular components of uterine fluid that are disturbed prior to implantation with a long term view to their possible manipulation to improve the chance of pregnancy in both natural and artificial cycles.

Collaborators

A/Prof Luk Rombauts, Monash IVF
A/Prof Beverley Vollenhoven, Monash IVF
WEHI Proteomics Laboratory