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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P275 | DOI: 10.1530/repabs.1.P275

Apoptosis and neutrophil infiltration in the human endometrium at menstruation, recapitulated in mouse model of induced menstruation

Gregory M Armstrong1, Alison Murray1, Jacqueline A Maybin1, Adriano G Rossi2 & Hilary O D Critchley1

1Queen’s Medical Research Institute, Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK; 2Queen’s Medical Research Institute, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.

Introduction: Menstruation is an inflammatory process characterised by tissue breakdown, bleeding and recruitment of leukocytes. Resolution of this inflammation at menses is critical both to limiting tissue damage and to efficient repair. Apoptosis and clearance of apoptotic cells are necessary for this process, and are thought to involve neutrophils.

Our aims were to (i) delineate neutrophil numbers and identify apoptosis in peri-menstrual endometrium and (ii) examine a mouse model of induced menstruation to determine if similar processes are present.

Materials and methods: Late secretory to early proliferative phase endometrial biopsies were collected with ethical approval from consenting women with regular cycles and no overt pathology. Cycle stage was determined by serum hormones, day of cycle and histology.

C57Bl/6J mice underwent induced menstruation using sequential oestrogen and progesterone exposure and uterine oil injections to effect decidualisation. Progesterone withdrawal induced bleeding.

Tissue sections were immunohistochemically-stained for cleaved caspase-3 (an apoptosis marker), and elastase, MPO and Gr-1 (human and mouse neutrophil markers). Caspase-3 activation was assessed by semi-quantitative histoscoring, while neutrophil abundance was determined by stereology microscopy and ImageJ.

Results and discussion: Immunostaining revealed increasing epithelial and stromal caspase-3 activation prior to menstrual bleeding, followed by a precipitous influx of neutrophils at menses. Apoptosis preceded leukocyte recruitment in both human and mouse endometrium, and is likely, as in other systems, to be crucial for resolution of inflammation.

We have demonstrated that this induced mouse menstruation model shows changes analogous to the human endometrium and is a useful model for future mechanistic studies.

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