PHI Research Team
Queensland Institute of Technology
University of Queensland
The endometrium is shed each month at menstruation and then restored in 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. We also hope to apply this knowledge to improve the treatment and healing of wounds and reduce scarring.
Scanning electron microscopy showing the endometrial surface on the first day of bleeding – and four days later when it has repaired without scarring.
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, we are applying our findings to identify factors useful in the treatment of wounds to improve scarring outcomes.
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 are also currently conducting an analysis of the protein signature of menstrual fluid. Our data suggests that menstrual fluid contains factors which aid endometrial repair after menstruation by enhancing the proliferation of these cells to cover a wounded surface.
Several molecules have been identified as enhancing or retarding endometrial repair. We are examining the underlying mechanisms controlling the actions of these molecules to better understand the scar-free aspects of endometrial healing.
National Health and Medical Research Council
- Developed and validated a mouse model for endometrial breakdown and repair
- Showed that matrix metalloproteinases are active during menstruation and responsible for the widespread tissue breakdown
- Shown that neutrophils and activin A are important for endometrial repair
- Endometrial repair occurs even in the absence of oestrogen
- Defined proteins present in menstrual fluid that regulate re-epithelialization of the endometrial surface
Evans J, Salamonsen LA. Inflammation, leukocytes and menstruation. Rev Endocr. Metab Disord DOI10-1007/s11154=012-9223-7
Evans J, Kaitu’u-Lino T, Salamonsen LA (2011) Extracellular matrix dynamics in scar-free endometrial repair: perspectives from mouse in vivo and human in vitro studies. Biol Reprod 85:511-523
Weisberg E, Hickey M, Palmer D, O'Connor V, Salamonsen LA, Findlay JK, Fraser IS (2009). A randomised controlled trial of treatment options for troublesome uterine bleeding in Implanon users. Human Reproduction (2009) 24(8):1852-1861
Kaitu'u-Lino TJ, Phillips DJ, Morison NB, Salamonsen LA (2009) A new role for activin in endometrial repair after menses. Endocrinology 150:1904-1911 ‘Recommended article' in F1000 Medicine.
Morison NB, Kaitu'u-Lino TJ, Fraser IS, Salamonsen LA. (2008) Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives. Reproduction 136(2):267-274
Hickey M, Salamonsen LA (2008) Endometrial structural and inflammatory changes with exogenous progestogens. Trends in Endocrinol Metabol 19:167-174.
Kaitu'u-Lino TJ, Morison NB, Salamonsen LA (2007) Estrogen is not essential for full endometrial restoration following breakdown: lessons from a mouse model. Endocrinology 148(10):5105-5111
Kaitu'u-Lino T, Morison N, Salamonsen L (2007) Neutrophil depletion retards endometrial repair in a mouse model. Cell Tissue Research 328(1):197-206