The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis
- PDF / 3,771,527 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 77 Downloads / 184 Views
BMC Research Notes Open Access
RESEARCH NOTE
The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis F. L. Cousins1,2* , J. K. Farley1, R. Kerrigan1, S. Mukherjee1,2, S. Darzi1,2, C. E. Gargett1,2 and J. A. Deane2*
Abstract Objective: Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endo‑ metriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial men‑ struation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. Results: Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis. Keywords: Endometrium, Endometriosis, Hedgehog signalling, Mouse model Introduction Endometriosis is a complex disorder of unknown aetiology, defined by the growth of endometrial fragments outside the uterine cavity. Endometriosis is thought to occur via the retrograde menstruation of endometrial fragments into the peritoneal cavity which then persist and form lesions on intra-peritoneal organs [1]. Retrograde menstruation occurs in 90% of menstruating females, yet only 10% go on to develop endometriosis, indicating that additional factors are involved [2]. Published data highlights that eutopic endometrial stromal cells from women with endometriosis exhibit increased adherence *Correspondence: [email protected]; [email protected] 1 The Ritchie Centre, Hudson Institute of Medical Research, 27‑31 Wright Street, Clayton, VIC, Australia 2 Department of Obstetrics and Gynaecology, School of Clinical Sciences At Monash Health, Monash University Faculty of Medicine, 246 Clayton Road, Clayton 3168, Australia
and proliferation in vitro [3, 4]. It is likely that cell signalling and cell growth pathways of eutopic endometrial cells are altered in women with endometriosis. Current non-surgical treatments for endometriosis are largely oral contraceptives, to limit retrograde menstruation and growth of established lesions, or analgesics for pain. Non-hormonal therapeutics are desperately needed and targeting cell signalling pathways may reveal new avenues for drug design. Hedgehog signalling is a developmental pathway that is activated in some endometrial cancers [5] and the endometrium of women with endometriosis [6]. Sonic hed
Data Loading...
