Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

MicroRNA-155 deficiency increases lesion development in a mouse model of endometriosis (#311)

Kavita Panir 1 , Erin Greaves 2 , John Schjenken 1 , Sarah Robertson 1 , Mary Louise Hull 1
  1. The Robinson Research Institute and The School of Medicine, The University of Adelaide, Adelaide, SA, Australia
  2. Developmental Biology, Endocrinology, Molecular Biology, The University of Edinburgh, Edinburgh, United Kingdom

Endometriosis, a benign gynaecological disorder affecting 10% of reproductive-aged women, is a condition in which endometrial cells from the lining of the uterus are found outside the uterine cavity, commonly presenting as lesions on the peritoneal wall or surface of the ovary. The exact mechanisms governing the development of this disease remain enigmatic, but have been linked to aberrant immune responses within the peritoneal cavity. MicroRNA-155 has been found to be upregulated in plasma samples from women with endometriosis, and is proposed to be involved in fibrosis and in promoting a pro-inflammatory immune environment.

In this study, we have generated a menstrual model of endometriosis in miR-155 deficient mice. This model utilises donor ovariectomised mice which are supplemented with oestrogen and progesterone to induce a ‘menstrual’ cycle. This ‘menstrual’ material is harvested and injected into a syngeneic recipient mouse. The development of endometriosis-like lesions are then evaluated at day 7 and 14 post-tissue transfer.

At one week following induction of endometriosis, miR-155 deficient mice had endometriotic-like lesions that were 4.98-fold heavier than that of genetically replete mice (C57/B6 control mice) (73.7mg vs 14.8mg, p<0.001). A corresponding 10.02-fold increase in lesion size was observed in miR-155 deficient mice compared to genetically replete mice (172.3 mm3 vs 17.2 mm3, p<0.001).  At day 14, lesion size and weight in both the control group and the mir-155 deficient group had decreased, indicative of the induction of the immune system to facilitate the clearance of ectopic endometrial tissue. However, the lesion weight (16.34mg vs 3.83mg, p<0.05) and size (39.56mm3 vs 2.5 mm3, p<0.01) in miR-155 deficient mice remained significantly higher when compared with the control mice.

Collectively, these results suggest that miRNA-155 modulation during ectopic lesion development may contribute to the pathology and progression of endometriosis, and could potentially be utilised for clinical therapeutics.