Project Leaders

• 
• 

During menstruation, the endometrium is shed and later restored during the next menstrual cycle. Resurfacing (reepithelialization) stops the bleeding and starts the restoration. Importantly, the endometrium is the only adult tissue to undergo rapid cyclic repair without scarring. We are working to understand the underlying mechanisms of endometrial repair to enable development of novel treatments for uterine bleeding problems in women, including those using progesterone based contraceptives and hormone therapy for menopause. A common gynaecological complaint, abnormal uterine bleeding is a major health issue for many women. Associated with a reduced quality of life, the condition can inhibit the undertaking of routine activities and work.

The mechanisms underlying normal uterine bleeding (menstruation: in which the endometrium is shed) and the tissue repair following menstruation are little understood. This is largely due to the fact that only humans and old world apes menstruate, making it very difficult to study. Long acting progestin-only contraceptives are also linked to abnormal uterine bleeding and spotting, with many women discontinuing use despite their effectiveness.  We have also been addressing this problem, initially in association with the World Health Organisation and the NIH and more recently with NHMRC funding.

Our work during the past 15 years has enabled understanding of the molecular mechanisms underlying menstruation. Our focus is now largely on the repair following menstruation, as we believe that this is the key to stopping normal and abnormal uterine bleeding. The endometrium is the only adult tissue able to repair itself without scarring. Thus as well as providing insights into female fertility and endometrial repair mechanisms. Importantly, this knowledge is proving of value also to improve the treatment and healing of wounds and reduce scarring.

We have developed two methods for investigating endometrial repair. These are a wound-healing assay in which we measure how quickly cultured endometrial cells can grow across a wound surface, and a method that measures the strength of the junctions between cells. Novel new technologies mean we can investigate the proliferation and migration of endometrial epithelium in real time. We have also established a multi-layered human skin ex vivo repair model, which is enabling translation of our findings to wound repair.

Following analysis of the protein signature of menstrual fluid using state-of-the art proteomics technologies, we have identified factors in menstrual fluid, which aid endometrial repair after menstruation by enhancing the proliferation of these cells to cover a wounded surface: these also act to improve wound healing in our skin models. We are now examining molecules we have identified as enhancing or retarding endometrial repair to understand the underlying mechanisms of the scar-free aspects of endometrial healing.

Collaborators:

Dr Leila Cuttle, Queensland Institute of Technology, WEHI Proteomics Laboratory
Dr Martha Hickey, University of Melbourne
Professor Susan Fisher, University of California, San Francisco, USA